Many reports describe an increased frequency and unusual features of endometrial polyps and carcinomas in women treated with tamoxifen (TMX) for breast cancer. Postmenopausal women with endometrial polyps were identified by computer search of pathology files from 1990 to 1996. Medical records were reviewed, and patients were divided into three groups: 28 receiving TMX for breast cancer, 23 receiving hormone replacement therapy (HRT), and 28 untreated controls (UC). Cumulative doses (CDs) of TMX were calculated. Histologic slides of polyps were reviewed blindly and evaluated for size, metaplasias, vascularity, fibrosis, and inflammation. Carcinomas were found in 3 TMX, no HRT, and 1 UC patient. Atypical hyperplasias were found in 1 TMX, 0 HRT, and 1 UC patient. Mean polyp size was larger in the TMX group (2.9 cm) than in the HRT (1.05 cm) and UC (1.35 cm) groups, and stromal fibrosis was more prominent in TMX-related and larger polyps. Mucinous metaplasias were observed more frequently in the patients receiving TMX. No other differences were noted. The two TMX patients in whom low-grade carcinomas developed and the one with atypical hyperplasia had independent risk factors. CDs for these patients were 32.9, 36.5, and 17.6 g, respectively. A high-grade carcinoma developed in a TMX patient without constitutional risk factors at a CD of 94.9 g. On the basis of a literature review and these results, low-grade carcinomas developing after relatively low CDs of TMX may be at least partially attributable to other risk factors. The association between poorly differentiated and nonendometrioid tumors with higher TMX CDs is still speculative, but the current study suggests that they may be related to TMX. A statistically significant increase in the frequency of thyroid replacement use by TMX patients is also noted.