We used the monoclonal antibody BR96 to determine the expression of the Lewis Y antigen in benign and malignant prostatic tissues. Strong immuno-staining was detected within the basal cells of benign glands in 29 of 30 specimens examined. In contrast, weak immuno-staining of the secretory (luminal) epithelium was detected in only 10 of these same 30 specimens. Moderate to strong immuno-staining of luminal cells, however, was observed in prostatic intraepithelial neoplasia in 15 of 17 specimens. Immuno-staining was detected within the malignant cells in all 49 specimens of primary prostatic adenocarcinoma examined. We used a semiquantitative technique to compare the extent of immuno-staining among well (combined Gleason score less than 6), moderately (combined Gleason score 6 to 7) and poorly (combined Gleason score more than 7) differentiated tumors as well as metastatic lesions. Poorly differentiated tumors demonstrated the greatest extent of immuno-staining compared to moderately and well differentiated adenocarcinoma. Strong immuno-staining was also detected within the malignant cells in 7 metastatic (5 nodal lesions and 2 bone marrow biopsies) tumors. The extent of immuno-staining in the metastatic lesions was similar to that observed in the poorly differentiated primary tumors. In summary, the Lewis Y antigen, as detected by BR96, is widely expressed within prostatic adenocarcinomas. Furthermore, the poorly differentiated as well as metastatic lesions frequently demonstrated the highest expression of the Lewis Y antigen. © 1995 American Urological Association, Inc.