The aim of the current study was to investigate the immunohistochemical expression of the retinoblastoma protein (pRB) in formalin-fixed, paraffin-embedded specimens obtained from 62 patients suffering from endometrial cancer. The avidin-biotin-peroxidase detection system with microwave pretreatment and the mouse anti-human NCL-RB1 monoclonal antibody were used. Heterogeneous nuclear immunostaining for the pRB was generally observed in the glandular cells in 59 out of 62 (95%) endometrial carcinomas, while stromal components were unreactive. In one case of stage Ic endometrioid adenocarcinoma, a small percentage of glandular cells (5%) stained positively with the anti-RB antibody, while two other tumors (stage IIa adenosquamous carcinoma and stage IIIa endometrioid adenocarcinoma) were pRB negative. In the cases with concomitant hyperplastic and neoplastic endometrial lesions, pRB immunoreaction was heterogeneous in the hyperplastic endometrial cells and in the adjacent neoplastic endometrium. Moreover, eight cases of endometrial carcinoma harboring K-ras codon 12 gene point mutation overexpressed pRB (more than 80% of glandular endometrial cells were positive) immunohistochemically, while none of three pRB negative slides had a K-ras gene alteration. Our data support the view that the pRB is expressed in most of the human endometrial neoplasms, but the lack of pRB immunoreactivity may correspond with the retinoblastoma gene rearrangements in a subset of advanced endometrial carcinomas.