Tamoxifen, a nonsteroidal antiestrogen with a partial estrogen-antagonist activity, is widely used as a hormonal adjuvant therapy for breast cancer in women with positive receptors for estrogens. Its prolonged administration has been associated with a series of collateral effects, among which the endometrial carcinoma is the most important. The aim of our study was to investigate an eventual correlation between a therapy with tamoxifen and the onset of endometrial lesions. We recruited 228 postmenopausal patients who had been operated on for breast cancer. They were divided into two groups according to the presence of positive or negative estrogen receptors. The group with positive receptors was subjected to hormonal adjuvant therapy by tamoxifen (20 mg/day for 5 years), while the group with negative receptors was not treated. All the patients underwent a hysteroscopic evaluation of the uterine cavity before and after treatment. The follow-up carried out 5 years later showed the presence of a statistically higher risk (p < 0.00001) of endometrial lesions, such as low glandular hyperplasia and polyps, than in the treated patients compared with untreated patients. On the other hand, because there was no onset of endometrial carcinoma, the risk of this kind of lesion turned out to be practically absent. In all the treated patients who did not evidence any endometrial lesions (n = 90) and in all those with negative receptors (n = 104) the endometrium seemed to have an atrophic aspect. In conclusion, according to these data, we believe that hormonal adjuvant therapy by tamoxifen (20 mg/day), associated with a periodic hysteroscopic evaluation, and eventually a directed biopsy of the endometrium in order to keep under control the frequent onset of benign endometrial lesions, does not absolutely seem to increase the risk of endometrial carcinoma.