Types of cancer of unknown primary

Cancer of unknown primary (CUP) means that cancer has already spread to other parts of the body, but doctors don’t know where it started (called the primary site).

Your healthcare team will take a sample of the tumour. The pathologist looks at the sample under a microscope to try to identify the type of cancer cell. The pathology report will also give your doctor information about how much the cancer cells look and act like normal cells. This is called differentiation. Differentiation is an important part of describing and identifying CUP.



well differentiated

The cancer cells look and act much like normal cells.

The cancer cells are slow growing and less likely to spread than cancer cells with higher grades.

moderately differentiated

The cancer cells don’t look and act exactly like normal cells.

The cancer cells are growing more quickly than well-differentiated cancer cells.

poorly differentiated

The cancer cells don’t look and act like normal cells.

The cancer cells tend to grow quickly and are more likely to spread than well or moderately differentiated cancer cells.


The cancer cells don’t look or act at all like normal cells.

The cancer cells tend to grow very quickly and are most likely to spread to other parts of the body.


Most cancers of unknown primary are carcinomas. Carcinoma is a type of cancer that starts in epithelial tissues. These tissues are a layer of cells that lines the body’s hollow organs and glands and makes up the outer layer of the skin. CUP is usually one of the following types of carcinoma.


Adenocarcinoma is the most common type of CUP. Adenocarcinoma is a type of cancer that starts in gland cells that make up the inner lining of some organs.

Adenocarcinoma of unknown primary is most often found in several places at the same time. The most common places it is found are the liver, lungs, lymph nodes or bones.

Most adenocarcinomas of unknown primary are well-differentiated or moderately differentiated tumours, but some are poorly differentiated or undifferentiated.

Poorly differentiated carcinoma

Poorly differentiated carcinoma is the second most common type of CUP. The cells are very abnormal. The pathologist believes it is a carcinoma but cannot tell what type of carcinoma it is. These tumours are most often found in younger people. Even though these tumours grow quickly, they may respond well to treatment.

Squamous cell carcinoma

Squamous cells are a type of epithelial cell. They are thin and flat and look like a fish scale. They are found in the epithelium that makes up the surface of the skin. They are also in the epithelium lining of other organs, such as the mouth, pharynx, esophagus, anus, cervix and vagina.

Squamous cell carcinoma of unknown primary is most often found in lymph nodes in the neck (called the cervical lymph nodes). The primary site may be somewhere in the head or neck (such as the mouth, throat or larynx) or in a lung.

Squamous cell carcinoma of unknown primary can also be found in lymph nodes in the groin (called the inguinal lymph nodes). The primary site may be in the anus, bladder, cervix, vagina, vulva or penis.

Extragonadal germ cell tumours

Germ cells are reproductive cells that develop into either sperm or eggs. They are usually found in the gonads, which are the testicles or ovaries. But sometimes they can be outside of the testicles or ovaries. When cancer starts in these cells, it is called an extragonadal germ cell tumour. (Extragonadal means outside of the gonads.)

Extragonadal germ cell tumours of unknown primary are usually found at the back of the abdomen (called the retroperitoneum) or in the middle of the chest (called the mediastinum).

Neuroendocrine carcinoma

Neuroendocrine carcinomas are different types of tumours that start in the neuroendocrine system. They are very rare. Only a very small number of CUPs are neuroendocrine carcinomas.

Experts think that many neuroendocrine carcinomas of unknown primary start in the pancreas.

Small cell carcinoma is a very aggressive type of neuroendocrine carcinoma that spreads quickly. Most small cell carcinomas of unknown primary are thought to start in the lung. These tumours are often found in many different parts of the body at diagnosis, but they respond well to chemotherapy.


Melanoma is a type of cancer that starts in melanocyte cells of the skin. Melanocytes make melanin. Melanin gives skin, hair and eyes their colour.

Melanoma of unknown primary is usually found in lymph nodes.

Undifferentiated tumours

If the pathologist tests the tumour but can’t identify it as any particular type of cancer, it is called an undifferentiated tumour, or neoplasm. Undifferentiated tumours are usually very aggressive tumours.

Expert review and references

  • American Cancer Society. Cancer - Unknown Primary. Atlanta, GA: 2014: https://www.cancer.org/.
  • Fizazi K, Greco FA, Pavlidis N, et al . Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. Oxford University Press; 2011.
  • Greco FA & Hainsworth JD . Cancer of unknown primary site. DeVita VT Jr, Lawrence TS, & Rosenberg SA. Cancer: Principles & Practice of Oncology. 10th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2015: 113:1720-1737.
  • Hainsworth JD, Greco FA . Neoplasms of unknown primary site. Hong WK, Bast RC Jr, Hait WN, et al (eds.). Holland Frei Cancer Medicine. 8th ed. People's Medical Publishing House; 2010: 120: 1713-1722.
  • Kim KW, Krajewski, KM, Jagannathan JP, et al . Cancer of unknown primary sites: what radiologists need to know and what oncologists want to know. AJR: American Journal of Roentgenology. The American Roentgen Ray Society; 2013.
  • National Cancer Institute. Carcinoma of Unknown Primary Treatment (PDQ®) Health Professional Version. 2015.
  • Pavlidis N, & Pentheroudakis G . Cancer of unknown primary site. Lancet. Elsevier; 2012.

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