Objectives: To assess the ultrasonographic appearance and associated pathological changes of the endometrium in postmenopausal breast cancer patients with tamoxifen therapy. Study design: Forty-eight postmenopausal breast cancer patients receiving 20 mg/day tamoxifen for 6-84 months (mean 29) and 38 control breast cancer patients without any hormonal treatment were examined by transvaginal ultrasonography and endometrial biopsy. Any thickening of the endometrium with cystic formations or homogeneous endometrial thickening > 10 mm detected by ultrasonography was defined as abnormal endometrial appearance. Homogenous endometrial thickening < 10 mm without cystic formations was accepted as normal. Statistical analysis was performed using the Student's t-test and Mann-Whitney U test. Results: The two groups were similar in age and menopausal period. The patients on tamoxifen therapy had a thicker endometrium (8.6 ± 6.6 mm) than the non- treated women (4.8 ± 3.1 mm), which was found to be a statistically significant difference (P < 0.01). The sonographic evaluations showed abnormal endometrial appearance in 8 cases of tamoxifen treated women while the others revealed homogeneous thickness < 10 mm without cystic formations or a thin linear echo with or without fluid in the endometrial cavity. All 8 patients with cystic appearance had endometrial thickness > 10 min. Only 1 patient had endometrial cancer on biopsy and no pathology was observed in the remaining 7 patients. In the control group, only 1 patient had abnormal ultrasonographic finding who had insufficient endometrial tissue on biopsy. Conclusions: Tamoxifen can produce a sonographic image of the endometrium that resembles endometrial neoplasia. It is suggested that the discrepancy between the sonographic findings and histology may be the result of the stromal edema of the endometrium from tamoxifen treatment. Until more data are gathered, all postmenopausal breast cancer patients who are being treated with tamoxifen should have a periodic ultrasonographic examination and those presenting with a sonogram suggestive of endometrial pathology should undergo biopsy.