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Cancer of Unknown Primary Stages

After someone is diagnosed with a cancer, doctors will try to figure out if it has spread, and if so, how far. This process is called staging. A cancer's stage is determined by examining tissue removed during an operation and sometimes imaging tests and physical exam. The stage describes how much cancer is in the body. It helps determine how serious the cancer is and how best to treat it. Doctors also use a cancer's stage when talking about survival statistics. Because cancer of unknown primary (CUP) is diagnosed after the cancer has already spread, all CUPs are considered advanced stage cancer.

Cancer staging can be complex, so ask your doctor to explain it to you in a way you understand.

How is the stage determined?

The staging system used for most cancers is the American Joint Committee on Cancer (AJCC) TNM system, which is based on 3 key pieces of information:

  • The extent (size) of the tumor (T): How large is the cancer? Has it grown into nearby structures or tissues?
  • The spread to nearby lymph nodes (N): Has the cancer spread to nearby lymph nodes?
  • The spread (metastasis) to distant sites (M): Has the cancer spread to other parts of the body?

Numbers or letters after T, N, and M provide more details about each of these factors. Higher numbers mean the cancer is more advanced.

Stage groupings

Once a person’s T, N, and M categories have been determined, this information is combined in a process called stage grouping to assign an overall stage. Most cancers have stages that range from I (1) through IV (4). As a rule, the lower the number, the less the cancer has spread. A higher number, such as stage IV, means cancer has spread more. Stage I is the least spread, and patients with this stage tend to have the best outlook. Stage IV cancers have the most spread and tend to have the poorest outlook.

Why cancers of unknown primary (CUP) are never stage I

For different types of cancer, each staging system is somewhat different. To determine a cancer’s stage, you first have to know where it started. Since the type of cancer is not known, it is difficult to accurately stage cancers of unknown primary (CUP). Nonetheless, to be considered a CUP, the cancer must have spread beyond the primary site. So, all CUPs are at least a stage II, and most  are stage III or IV.

The most recent American Joint Committee on Cancer (AJCC) staging system, effective January 2018, applies to cancer that is found in the lymph nodes of the neck, but the primary cancer has not been found. This is considered a CUP, but since most of these cancers are thought to start in the head and neck area they are treated as such. If your cancer fits this description, it is best to talk to your doctor about your specific stage.

Even though a patient’s exact stage may not be known, it’s still possible to make some predictions about prognosis (outlook) based on which organs are affected by the cancer. For example, if the cancer is only found in lymph nodes in one area or in a single organ, the outlook tends to be better than if the cancer is found in many different organs. Of course, other factors, such as how well the cancer responds to treatment and a person’s overall health also play a role.

 

 

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Developed by the American Cancer Society medical and editorial content team with medical review and contribution by the American Society of Clinical Oncology (ASCO).

Greco FA, Hainsworth JD. Carcinoma of Unknown Primary In: DeVita VT, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 10th ed. Philadelphia, PA: Lippincott Williams & Wilkins 2015: 1719-1736.

National Cancer Institute. Physician Data Query (PDQ). Cancer of Unknown Primary Treatment. 05/06/2024. Accessed at: https://www.cancer.gov/types/unknown-primary/hp/unknown-primary-treatment-pdq on April 22, 2025.

National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Occult Primary (Cancer of Unknown Primary). v.2.2025. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/btc.pdf on April 22, 2025.

Last Revised: May 27, 2025

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