Given their frequent expression in breast and gynecologic carcinomas, the National Comprehensive Cancer Network has recommended that the immunohistochemical expression of estrogen (ER) and/or progesterone (PR) receptors in a carcinoma of unknown primary can be used to support a breast or gynecologic origin. Several reports in the literature, however, have described such expression in a variable proportion of nonmammary and nongynecologic carcinomas. The aim of this study was to systematically evaluate the immunohistochemical expression of ER and PR on tissue microarray sections representing 348 nonbreast or gynecologic and nongynecologic tumors of lung, esophageal, gastric, pancreatic, colonic, renal, or bladder origin. We also performed a pooled analysis of the published literature in this regard. Except for 1 (2.5%) out of 40 pancreatic adenocarcinomas that expressed PR, there was no ER or PR expression in any of the other tumors evaluated by immunohistochemistry. A pooled literature review demonstrated that most of the evaluated tumors express ER and/or PR in up to 3% of cases, whereas some lung and bladder carcinomas showed such expression in around 10% of cases. This literature review also demonstrated that the frequency of ER and PR expression was dependent on the antibody clone used. Given that ER and PR expression can occasionally be seen in carcinomas of nonmammary/nongynecologic origin, we conclude that the diagnosis of metastatic breast, ovarian or endometrial carcinoma in a carcinoma of unknown primary should not be based solely on such expression. © 2009 Lippincott Williams & Wilkins, Inc.