Small cell carcinoma of unknown primary (SCUP) is an uncommon cancer that is usually diagnosed in the lymph nodes, liver, brain, or bone. Historically, this neoplasm has always been included with extrapulmonary small cell carcinomas (EPSCCs). The true incidence of SCUP is unknown but has been reported to comprise between 7% and 30% of EPSCCs. Although identification of small cell carcinoma can usually be made with histologic examination and immunohistochemical stains, differentiation between primary, metastatic, or other neuroendocrine tumors can be challenging. The prognosis of SCUP varies from a few months to several years depending on the location, extent of disease, and response to therapy. Combination chemotherapy with regimens similar to those used in small cell lung cancer (SCLC) form the backbone of therapy. However, multimodality therapy, including surgery and/or radiation therapy, in addition to chemotherapy may be used to treat localized disease. This review examines the biology, evaluation, and treatment of SCUP.