Cancer of Unknown Primary Origin
Cancer of Unknown Primary Origin
This fact sheet was reviewed on 1/22/04
National Cancer Institute Fact Sheet

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.

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.

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 Web site at or from the Cancer Information Service
(see below).

Related Topics
Publications (available on
• National Cancer Institute Fact Sheet 6.7, Cancer: Questions and Answers
• National Cancer Institute Fact Sheet 6.20, Metastatic Cancer: Questions and
• What You Need To Know About™ 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
NCI’s Web site:
LiveHelp, NCI’s live online assistance:
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