Seven-hundred thirty-seven asymptomatic postmenopausal breast cancer patients under long-term adjuvant tamoxifen therapy (average, 50 months) were screened by endometrial ultrasonography. Abnormal endometrial thickness (6 mm or larger) was observed in 209 subjects and was significantly associated with patients' age and duration of tamoxifen therapy. Outpatient endometrial biopsy was recommended in presence of abnormal endometrial thickness: 25 subjects refused biopsy, whereas 76 were not biopsied because of cervical stenosis and were followed-up by repeat sonography. Of 108 biopsied subjects, one case of endometrial carcinoma (as expected in the screened cohort according to age-specific incidence rates provided by the regional cancer registry) and one case of endometrial hyperplasia were histologically confirmed, whereas endometrial atrophy was evident in the remaining cases. No other case of endometrial carcinoma has been recorded so far in the studied cohort according to the local cancer registry and no further change of the endometrium has been observed at sonographic follow-up. The cohort will be followed-up by repeat annual endometrial sonography. Thus far, we did not find evidence of increased prevalence of endometrial pathology (carcinoma or hyperplasia) which may be ascribed to tamoxifen therapy. The apparent increase in endometrial thickness observed at sonography might be explained by tamoxifen-induced changes of endometrial stroma and myometrium, misinterpreted as hyperplasia, while causing no real epithelial disease.