Carcinoma of unknown primary is common, accounting for 2-6% of all cancer patients. The primary site is found in less than 25% of patients before death and frequently goes undiscovered at postmortem examination. At the time point of first diagnosis of CUP syndrome, usually more than 80% of the patients present a disseminated situation. Prognosis depends on the involved site and is unaffected by whether or not the primary site is ever found. For patients presenting with metastasis to peripheral lymph nodes, node dissection may be curative. In patients with small cell malignancies, peritoneal carcinomatosis (in women), poorly differentiated carcinomas involving external lymph nodes, mediastinum, or retroperitoneum, but without metastases to viscera or bone, objective long-term responses are possible with combination chemotherapy. For all other patients, toxic therapies are recommended only for patients with good functional status, for palliation of symptoms when they develop, and for continuous support of the quality of life.