Types of cancer of unknown primary

Cancers are usually grouped by where they first started (the primary tumour), such as breast cancer or lung cancer. Doctors can also group cancers by type of cell they start from. For cancer of unknown primary (CUP), there are 5 main types. 

Tests to look for the type of cancer cells

Tests can give doctors useful information about the cancer, even when they can't find a primary tumour. Doctors can also get important clues about the cancer from:

  • your gender
  • the position of the secondary cancer
  • detailed laboratory information about the cancer cells 

Laboratory tests

To find out what type of cell the cancer started, your doctor takes a tissue sample (biopsy) and sends it to the laboratory. The doctor in the lab (pathologist) uses a microscope to look at the shape and structure of the cells. 

They may also test the tissue sample using antibodies to look for tumour markers. Tumour markers are chemicals produced by some cancer cells. Some tumour markers are made by only one type of cancer, while others can be made by several different types of cancer.

The study of tumour markers is called immunohistochemistry (IHC). Tumour markers are often called IHC markers.

With CUP, knowing the type of cell gives doctors a clue where the cancer is most likely to have started from. They use this information to help plan your treatment.

Types of CUP

CUP can be grouped into 5 main groups.


Adenocarcinoma starts in the gland cells. These cells line certain organs of the body, and release substances such as mucus or digestive juices. At least 60 out of 100 CUP (60%) are adenocarcinomas. 

The most common places for secondary cancers are the lymph nodes, liver, lung and bone. 

Squamous cell carcinoma

Squamous cells are flat cells found in the skin and in the lining of parts of the body such as:

  • nose
  • throat
  • lungs
  • cervix
  • back passage (anus)

The secondary tumours are usually noticed as swollen (enlarged) lymph nodes in the neck or groin. Around 5 out of 100 CUP (5%) are squamous cell tumours. 

Neuroendocrine tumours

About 3 out of 100 CUP (3%) are neuroendocrine tumours (NETS). They mainly start in the small bowel or other parts of the digestive system. But they can also occur in the lung, pancreas, kidney, ovary or testicles.

Some neuroendocrine tumours respond very well to treatment.

Poorly differentiated carcinoma

This type of cancer starts in cells that make up the tissue that covers the outside of the body and lines the internal organs (epithelial cells). Doctors usually can't tell exactly what type of epithelial cells the cancer started in. This is because the cells look so different from normal cells.

Around 30 in 100 CUP (30%) are poorly differentiated carcinoma.

Poorly differentiated neoplasm

The cells of the tumour look so abnormal the doctor can’t tell what type of cell the cancer started in. About 5 out of 100 CUP (5%) are this type. But after further testing in the lab, some of these turn out to be carcinomas or other types of cancer such as lymphoma or melanoma.

Other CUP types

Occasionally cancers such as melanoma, sarcoma and germ cell tumours are diagnosed without finding the primary tumour. Doctors treat them following guidelines for these specific types of cancer, and not CUP.

Last reviewed: 
20 May 2021
Next review due: 
20 May 2024
  • Cancers of unknown primary site: ESMO clinical practice guidelines for diagnosis, treatment and follow up
    K Fizazi and others
    Annals of Oncology, 2015. Vol 26, Supplement 5

  • Cancer: Principles and Practice of Oncology (10th edition)
    VT DeVita , TS Lawrence, SA Rosenberg
    Lippincott, Williams and Wilkins, 2015

  • Cancer and its Management (7th edition)
    J Tobias and D Hochhauser
    Wiley-Blackwell, 2015

  • Adenocarcinoma of unknown primary site 
    BMJ Best Practice. Last accessed May 2021

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