Forty-six primary vaginal carcinomas were examined immunohistochemically for expression of retinoblastoma (RB) protein, epidermal growth factor receptor (EGFR), and c-erbB-2 oncoprotein. The results demonstrated that RB protein was not lost in any of the cases, suggesting that structural abnormalities of the RB gene may not play an important role in the pathogenesis of vaginal carcinoma. Fifteen and 11% of the cases showed increased expression of EGFR and c-erbB-2 oncoprotein, respectively, indicating that these oncoproteins may be involved in the neoplastic process of a minority of vaginal carcinomas. Overexpression of EGFR and c-erbB-2 oncoprotein had no prognostic significance in vaginal carcinomas.