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Cancer of Unknown Primary Origin 

Cancer can begin in any organ or tissue of the body. The primary, or original, tumor is 

usually named for the part of the body or the type of tissue in which the cancer begins. The 

disease can spread (metastasize) from the primary tumor and form metastatic tumors in other 

parts of the body. For example, breast cancer cells can metastasize to the lungs and cause the 

growth of a new tumor. When this happens, the tumor in the lung is called metastatic breast 

cancer because it is composed of breast cancer cells, not lung cancer cells. 

Each year in the United States, several thousand people are diagnosed with metastatic 

cancer whose primary cancer site is not known. When the primary site cannot be identified, this 

Key Points 

• Cancer of unknown primary (CUP) origin is the diagnosis when 

metastatic cancer is found but the place where the cancer began (the 

primary site) cannot be determined. 

• About 2 to 4 percent of all cancer patients have a cancer whose 

primary site is never identified. 

• Treatment for CUP depends on many factors, including where the 

metastatic cancer is found, what the cancer cells look like under a 

microscope, and the patient’s age and general health. 

• Recent advances in diagnostic techniques have improved doctors’ 

ability to eventually find the primary site, even when the original 

diagnosis is CUP. 
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disease may be called carcinoma of unknown primary (CUP). Most often, the metastatic cancer 

is first found in the lymph nodes, liver, lung, or bone. 

In recent years, microscopic and other diagnostic techniques have improved dramatically. 

For this reason, doctors can now determine the primary site in about four out of five cases first 

diagnosed as CUP. In some cases, the part of the body where cancer cells are first found helps 

the doctor decide which diagnostic tests will be most helpful. Doctors also have other clues that 

help them find the primary site: 

• The pattern of spread may suggest the location of the primary site. When the metastatic 

cancer is found in the upper part of the body, the original site is likely to be above the 

diaphragm (the thin muscle under the lungs that separates the chest from the abdomen) at 

sites such as the lung and breast. If the metastatic cancer appears first in the lower part of the 

body, the primary cancer is likely to be at sites below the diaphragm, such as the pancreas 

and liver. 

• The type of cell found in the metastatic cancer can also provide clues about the hidden 

 primary site. 

 Most patients with an unidentified primary tumor have a cell type called adenocarcinoma. 

The term adenocarcinoma refers to cancer that begins in the cells in glandular structures in the 

lining or covering of certain organs in the body. Common primary sites for adenocarcinomas 

include the lung, pancreas, breast, prostate, stomach, liver, and colon. 

When the cancer cells are poorly differentiated (that is, they look very different from 

normal cells when viewed under a microscope), the cancer may be either a lymphoma or a germ 

cell tumor. Lymphomas begin in the lymphatic system (a grouping of lymph glands and lymph 

vessels found throughout the body that participates in the defense against attack from bacteria, 

viruses, or other agents); germ cell tumors usually begin in the ovaries and testes. 
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In patients in whom the primary cancer is eventually found, the lung and pancreas are the 

most common primary cancer sites. CUP also may be traced to the breast, prostate, colon, or 

rectum as the primary site. 

Sometimes, however, even when doctors use very sophisticated methods to try to identify 

the primary site, the part of the body the cancer cells came from cannot be determined. About 

2 to 4 percent of all cancer patients have a cancer whose primary site is never found. 

 Identifying the primary tumor site is important because knowing its location and type 

often helps doctors plan the best treatment. Treatment that is specific to the suspected type of 

cancer is likely to be more effective. Still, when diagnostic tests have not identified the primary 

site, doctors must decide whether the potential benefits of more extensive testing outweigh a 

patient’s discomfort and the financial costs. 

 CUP is a term that refers to many different cancers. For that reason, treatment depends 

on where the cancer is found, what the cancer cells look like under a microscope, and the 

patient’s age and overall physical condition. No method is standard, but chemotherapy, radiation 

therapy, hormone therapy, and surgery may be used alone or in combination to treat patients who 

have CUP. Even when the cancer is unlikely to be cured, treatment may help the patient live 

longer or improve the patient’s quality of life. However, the potential side effects of the 

treatment must be considered along with the potential benefits. 

 The National Cancer Institute is currently supporting clinical trials (research studies) of 

new treatments for CUP. Information about ongoing studies is available on the NCI’s 

Cancer.gov Web site at http://cancer.gov/clinical_trials or from the Cancer Information Service 

(see below). 
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Related Topics

Publications (available on http://cancer.gov/publications) 

• National Cancer Institute Fact Sheet 6.7, Cancer: Questions and Answers

• National Cancer Institute Fact Sheet 6.20, Metastatic Cancer: Questions and 

Answers

• What You Need To Know AboutTM Cancer

National Cancer Institute (NCI) Resources

Cancer Information Service (toll-free)

 Telephone: 1–800–4–CANCER (1–800–422–6237) 

 TTY: 1–800–332–8615 

Online 

NCI’s Web site: http://cancer.gov 

LiveHelp, NCI’s live online assistance: 

https://cissecure.nci.nih.gov/livehelp/welcome.asp 

 

This fact sheet was reviewed on 1/22/04