Diagnosis of multiple myeloma

Diagnosing multiple myeloma usually begins with a visit to your family doctor. Your doctor will ask you about any symptoms you have and do a physical exam. Based on this information, your doctor may refer you to a specialist or order tests to check for multiple myeloma or other health problems.

The process of diagnosis may seem long and frustrating. It’s normal to worry, but try to remember that other health conditions can cause similar symptoms as multiple myeloma. It’s important for the healthcare team to rule out other reasons for a health problem before making a diagnosis of multiple myeloma.

The following tests are commonly used to rule out or diagnose multiple myeloma. Many of the same tests used to diagnose cancer are used to find out the stage, which is how far the cancer has progressed. Your doctor may also order other tests to check your general health and to help plan your treatment.

Health history and physical exam

Your health history is a record of your symptoms, risk factors and all the medical events and problems you have had in the past. In taking a health history, your doctor will ask questions about a personal history of:

  • symptoms that suggest multiple myeloma
  • abnormal blood or urine test results

Your doctor may also ask about a family history of blood-related conditions including multiple myeloma.

A physical exam allows your doctor to look for any signs of multiple myeloma. Find out more about a physical exam.

Complete blood count (CBC)

A CBC measures the number and quality of white blood cells, red blood cells and platelets. Myeloma cells (abnormal plasma cells) prevent these normal blood cells from developing in the bone marrow. A CBC is done to see if there is a shortage of these cells in the blood, which may lead to:

  • anemia (a low red blood cell count)
  • bleeding problems (caused by a low platelet count)
  • weakened immune system and infections (caused by low white blood cell count)

Find out more about complete blood count (CBC)..

Blood chemistry tests

Blood chemistry tests measure certain chemicals in the blood. They show how well certain organs are functioning and can help find abnormalities. The following substances and chemicals may be found in abnormal amounts in people with multiple myeloma:

  • protein
  • creatinine
  • albumin
  • calcium
  • alkaline phosphatase
  • uric acid
  • beta-2-microglobulin
  • lactate dehydrogenase (LD)

Find out more about blood chemistry tests.

Quantitative immunoglobulin (Ig) test

A quantitative immunoglobulin (Ig) test measures the amount of different antibodies (special types of protein molecules that are also called immunoglobulins) in the blood to check if they are high or low. There are 5 types of immunoglobulins – IgA, IgD, IgE, IgG and IgM. A high level of one of these immunoglobulins is often present in multiple myeloma. IgG and IgA are the immunoglobulins most often found in high amounts in people with multiple myeloma.

Protein electrophoresis

Protein electrophoresis is a method that separates proteins in the blood or urine. Electrophoresis is a test used to find:

  • abnormal proteins
  • missing proteins
  • protein levels that are too high or too low

In people with multiple myeloma, 70% have high levels of IgG protein, 20% have high levels of IgA and 5–10% produce only immunoglobulin light chains (Bence-Jones proteins).

Serum protein electrophoresis (SPEP)

SPEP checks for the presence of M-protein in the blood. M-protein is an immunoglobulin that is found in high amounts in a person with multiple myeloma.

Urine protein electrophoresis (UPEP)

UPEP checks for the presence of M-protein in urine that has been collected over 24 hours. UPEP can also detect part of an M-protein called an immunoglobulin light chain (also called a free light chain or Bence-Jones protein).


Immunofixation is a specialized type of electrophoresis that identifies the type of M-protein or immunoglobulin light chain that is found by SPEP or UPEP.

Serum free light chain test

A serum free light chain test looks for immunoglobulin light chains (called free light chains or Bence-Jones proteins) in the blood. This can be helpful in diagnosing multiple myeloma if an M-protein isn’t found by SPEP.  

A serum free light chain test also measures the light chain ratio. The light chain ratio shows if the amount of each light chain is out of balance, which can be a sign of multiple myeloma. Immunoglobulins have 2 types of light chains – kappa and lambda. Free light chains are normally found in about the same amounts.


A urinalysis is a routine urine test that describes the colour, appearance and contents of a urine sample. A urinalysis may be used to measure the amount of protein in the urine.

A doctor will usually get you to collect your urine over a 24-hour period. UPEP may be used to check for Bence-Jones proteins in the sample. A large amount of Bence-Jones protein may damage the kidney.

Find out more about urinalysis.


During a biopsy, the doctor removes tissues or cells from the body so they can be tested in a lab. The report from the lab will confirm whether or not cancer cells are present in the sample.

The most common type of tissue biopsy for diagnosing multiple myeloma is a bone marrow aspiration and biopsy. Doctors may also do a biopsy test for amyloid if they are having trouble diagnosing multiple myeloma.

Bone marrow aspiration and biopsy

During a bone marrow aspiration and biopsy, cells are removed from the bone marrow so they can be looked at under a microscope. The report from the lab will confirm whether or not there are abnormal plasma cells in the sample. The report will also give the percentage of plasma cells out of all of the cells in the bone marrow.

Tissue collected during a bone marrow aspiration and biopsy can also be sent for other tests such as cytogenetic tests, immunohistochemistry and flow cytometry.

Find out more about bone marrow aspiration and biopsy.

Biopsy for amyloid

Amyloid refers to a protein or part of a protein that forms abnormal clumps in the body. In light chain amyloidosis, the light chains of an immunoglobulin build up in tissues of the body (called amyloid deposits). Amyloid can build up in any tissue and interfere with its function. Light chain amyloidosis is a condition that may affect people with multiple myeloma.

Amyloid is sometimes seen on a bone marrow biopsy sample, but a doctor may biopsy other tissues, such as the fat on the abdomen (belly), to look for amyloid. In rare cases, a doctor will biopsy the heart or kidneys to look for amyloid. This is only done if it isn’t clear why a person is having heart or kidney problems.

Learn about light chain amyloidosis.

Other tissue biopsies

Doctors may also biopsy other suspicious areas of the body, including:

  • an abnormal area of a bone found on an x-ray – to look for a plasmacytoma
  • a tumour outside the bone – to look for an extramedullary plasmacytoma

Cytogenetic tests

Cytogenetics is the study of a cell’s chromosomes, including the number, size, shape and how they are arranged. Cytogenetic tests (chromosomal analysis) show chromosomal changes which affect some people with multiple myeloma. The results of cytogenetic studies also help doctors plan treatment and predict how well the treatment will work.

Cytogenetic tests used in people with multiple myeloma include karyotyping and fluorescence in situ hybridization (FISH).


A doctor looks for changes in chromosomes in cells from a sample of blood or bone marrow. Karyotyping can find large chromosomal changes like a missing part of a chromosome or an entire missing chromosome. Chromosome 13 is sometimes deleted (missing) in people with multiple myeloma. Karyotyping can also find small chromosomal changes like a rearranged chromosome. Chromosome 14 is commonly rearranged (called a translocation) in people with multiple myeloma. The results of karyotyping take up to 2–3 weeks because the cells have to be grown in the lab before they are tested.

Fluorescence in situ hybridization (FISH)

Some major chromosomal changes can be found by looking at cells under a microscope. But most changes in DNA need a closer analysis through other molecular techniques. FISH is a specific molecular genetic test used to find chromosomal changes and other genetic changes in cells using special DNA probes labelled with fluorescent dyes. FISH can find small chromosomal changes like a missing or rearranged chromosome. FISH test results only take a couple of days because the cells don’t have to be grown in the lab before they are tested.


Immunohistochemistry is a test that uses special stains to look at details in a cell. Immunohistochemistry can test for specific proteins that are often found in people with multiple myeloma. This gives the doctor more information than routine stains, which are used to look at the size and shape of cells.

Flow cytometry

Flow cytometry is a lab test that is used to sort, count and examine microscopic particles (such as cells or DNA). Cells can be measured by staining them with a light-sensitive dye bound to antibodies, placing them in fluid and passing them through a laser beam. The laser makes these cells give off a light that is measured and analyzed by a computer. It allows data to be collected rapidly from thousands of cells in a single sample.

Flow cytometry can help doctors tell the difference between abnormal plasma cells (called myeloma cells) and normal plasma cells.


An x-ray uses small doses of radiation to make an image of the body’s structures on film. Most bones in the body are x-rayed when diagnosing multiple myeloma. This is called a skeletal survey. X-rays are used to:

  • check for broken or weakened bones in the skull, spine, legs, arms, ribs and pelvis
  • check for areas of the bone that may indicate a plasmacytoma (a collection of myeloma cells in one location that forms a single tumour)
  • measure bone loss (bone mineral density)

Find out more about x-ray.


Magnetic resonance imaging (MRI) uses powerful magnetic forces and radiofrequency waves to make cross-sectional images of organs, tissues, bones and blood vessels. A computer turns the images into 3-D pictures. MRI is used to:

  • look for changes to the bone marrow
  • check for broken or weakened bones
  • look for a plasmacytoma
  • check for spinal cord compression

Find out more about MRI.

MRI-guided fine needle aspiration

MRI may also be used to help guide the needle while performing a fine needle aspiration (FNA) of a suspected plasmacytoma. Cytogenetic tests can then be done on the cells that are removed.

Find out more about fine needle aspiration.

CT scan

A computed tomography (CT) scan uses special x-ray equipment to make 3-D and cross-sectional images of organs, tissues, bones and blood vessels inside the body. A computer turns the images into detailed pictures. A CT scan is used to:

  • check for broken or weakened bones
  • look for a plasmacytoma

Find out more about CT scan.

CT-guided fine needle aspiration

A CT scan may also be used to help guide the needle while performing a fine needle aspiration of a suspected plasmacytoma. Cytogenetic tests can then be done on the cells that are removed.

PET scan

A positron emission tomography (PET) scan uses radioactive materials called radiopharmaceuticals to look for changes in the metabolic activity of body tissues. A computer analyzes the radioactive patterns and makes 3-D colour images of the area being scanned. A PET scan is sometimes used to:

  • look for changes to the bone marrow
  • look for a plasmacytoma

Find out more about PET scan.

PET-CT scan

A PET-CT scan combines a CT scan and a PET scan. A PET-CT is sometimes used to:

  • look for bones at risk of fracture in people with normal x-rays
  • look for plasmacytomas inside and outside of the bones

Questions to ask your healthcare team

To make the decisions that are right for you, ask your healthcare team questions about diagnosis.

Expert review and references

  • Alberta Health Services. Multiple Myeloma Clinical Practice Guideline LYHE-003. Alberta Health Services; 2015.
  • American Cancer Society . Multiple myeloma . Atlanta, GA : American Cancer Society ; 2014 : https://www.cancer.org/.
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  • Myeloma Canada. Multiple Myeloma Patient Handbook. Third ed. Kirkland, QC: Myeloma Canada; 2014.
  • National Cancer Institute. Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment PDQ®: Patient Version. National Cancer Institute; 2015: http://www.cancer.gov/cancertopics/pdq/treatment/myeloma/Patient.
  • National Cancer Institute. Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment PDQ®: Health Professional Version. National Cancer Institute; 2014: http://www.cancer.gov/cancertopics/pdq/treatment/myeloma/healthprofessional.
  • National Comprehensive Cancer Network. Multiple Myeloma (Version 4.2015). National Comprehensive Cancer Network; http://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf.
  • Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, et al . International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncology.
  • Rajkumar SV, Kyle RA . Diagnosis and treatment of multiple myeloma. Wiernik PH, Goldman JM, Dutcher JP, Kyle RA (eds.). Neoplastic Diseases of the Blood. 5th ed. Springer; 2013: 33: 637-664.
  • The Leukemia & Lymphoma Society. Myeloma. Revised ed. White Plains, NY: The Leukemia & Lymphoma Society; 2013: http://www.llscanada.org/content/nationalcontent/resourcecenter/freeeducationmaterials/myeloma/pdf/myeloma.pdf.

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