The retinoblastoma (RB) gene was the first defined tumor suppressor gene. While originally described in retinoblastoma, more recently alterations in RB have been described in a number of other human neoplasms and there has been a suggestion that alteration of RB may play a significant role in the development of endometrial carcinoma. We examined RB protein expression by immunohistochemistry in a series of cases including normal endometrium, endometrial hyperplasia, and endometrial carcinoma. A relatively homogeneous pattern of staining was observed in proliferative endometrium, while weak or absent reactivity was noted in secretory endometrium. A heterogeneous pattern of reactivity was observed in 10/10 cases of hyperplasia, 66/70 cases of endometrial adenocarcinoma, and 7/7 cases of uterine carcinosarcoma. An altered pattern of reactivity was observed in the remaining 4/70 cases of adenocarcinoma. All of the cases with altered reactivity were high grade neoplasms. We conclude that alteration of RB protein expression is uncommon in endometrial adenocarcinoma and when it does occur, it may represent a late event in carcinogenesis.