Seven cases of endometrial adenocarcinoma patients who had experienced long-term tamoxifen treatments as adjuvant therapy of breast carcinoma, were investigated with respect to estrogen receptor (ER) status. Four cases of endometrial adenocarcinoma without tamoxifen treatment but with a previous history of breast carcinoma were investigated for comparison. One of the 7 and two of the 4 cases were positive for ER immunohistochemically. Thus, the frequency of ER positivity in secondary endometrial adenocarcinoma seemed to be at random among tamoxifen-treated and non-treated breast cancer patients. These results suggest that tamoxifen-mediated human endometrial carcinogenesis may not involve estrogenic pathway(s) but may involve other carcinogenic mechanisms such as DNA adduct formation as shown in rat liver tumorigenesis.