We reviewed the clinical history and pathology material of 72 patients seen at the M. D. Anderson Cancer Center who developed malignant neoplasms of the uterine corpus after being treated for breast carcinoma with either tamoxifen or other therapeutic regimens. The purpose of this study was to investigate the type of malignant tumors seen in the uterus, their association with endometrial polyps or hyperplasia, and their possible relationship to tamoxifen treatment. This study shows that in patients treated for breast carcinoma, the uterine malignancies are characterized by several features: (a) a previously unreported high incidence of clear cell carcinoma (14 cases) and leiomyosarcoma (12 cases); (b) seven of 12 leiomyosarcomas with unusual features, such as epithelioid (5), tubular (1), and myxoid features (2); (c) a higher incidence of serous carcinoma (45% in patients treated for > or = 12 months); (d) endometrial polyps associated with carcinoma more often than endometrial hyperplasia.