Cancer of Unknown Primary Origin

Cancer of Unknown Primary Origin

Pictured: Robert Motzer

Compassionate, Expert Care -- For patients with tumors that are hard to diagnose because the site of origin is unknown, we have a specialized team in place, which includes medical oncologist Robert Motzer.

Cancer can develop anywhere in the body. The organ or region of the body where cancer begins is known as the primary site. Cancer — including cancer that metastasizes, or spreads, to form new tumors elsewhere in the body — is named after the primary site. For example, colon cancer that spreads to the liver is called metastatic colon cancer, rather than liver cancer, because it contains colon cancer cells.

According to the American Cancer Society, an estimated 2 to 5 percent of all cancer patients have metastatic (secondary) tumors for which routine testing cannot locate the primary site. This is called cancer of unknown primary origin (CUP). Patients may be diagnosed with cancer of unknown primary origin if the primary tumor is too small to be identified with routine imaging tests, it regresses (disappears) before a secondary tumor arises, or the secondary tumor has several possible primary sites. Occasionally, a primary tumor is discovered during surgery to treat other conditions.

Cancer of unknown primary origin can appear anywhere in the body, but is most commonly found in the lymph nodes, liver, lungs, bones, or skin.

Types of Cancer of Unknown Primary Origin

There are four types of cancer of unknown primary origin. A pathologist can determine the cancer type by observing the tumor’s cells under the microscope.

Approximately 60 percent of tumors designated as cancer of unknown primary origin are adenocarcinomas, which are made of epithelial cells from a gland (glands are tissues that produce substances within and outside of the body). Epithelial cells form the lining of most internal organs, making it difficult to identify the primary tumor site. Common primary sites for adenocarcinomas include the lungs, pancreas, breast, prostate, stomach, liver, and colon.

Approximately 20 to 30 percent of all CUP tumors contain poorly differentiated cancer cells, which do not resemble normal cells and are usually more aggressive than other cancer cells. More specialized testing may indicate whether these tumors began in lymph cells, skin cells, neuroendocrine cells, or other specialized cells. However, many poorly differentiated cancer cells appear so different from normal cells that doctors cannot determine their original cell type.

Squamous cell carcinomas, which account for less than 10 percent of CUP tumors, are made of the flat epithelial cells that are found on the surface of skin or in the lining of certain organs.

Some cancers of unknown primary origin contain neuroendocrine cells, a highly diverse group of cells that contain and/or produce certain hormones. Neuroendocrine carcinoma can begin anywhere in the body, which can make it difficult to identify the primary site. For more information about neuroendocrine tumors, visit Gastrointestinal Neuroendocrine Tumors and Pulmonary Neuroendocrine Tumors.


Symptoms of a cancer of unknown primary origin are usually noticed in the area in which the tumor is found, such as the lungs, liver, bones, or lymph nodes. However, some patients have no symptoms, and only learn they have cancer following a medical or imaging test. Others experience symptoms that could result from a variety of other health conditions.

If symptoms occur, they may include:

  • pain in a specific area of the body, such as the chest, abdomen, or bones
  • loss of appetite
  • weight loss
  • a lump in any part of the body, including the lymph nodes
  • persistent cough or hoarseness
  • changes in bowel or bladder habits
  • persistent fever or night sweats