Prostate stem cell antigen (PSCA) is a GPI-anchored membrane protein whose expression is reportedly up-regulated in a majority of human prostate cancers, including advanced stages and metastases. In this study, we investigate the expression pattern of the murine orthologue of PSCA by in situ hybridization in fetal and adult mouse tissues. Murine PSCA is expressed during fetal development in the urogenital sinus, skin, and gastrointestinal tract. The expression in these tissues is restricted to the most superficial cell layer. In the adult mouse, expression is highest in the mucosal lining of the urinary tract. In the normal adult prostate, expression of PSCA is detected exclusively in the secretory epithelium. Examination of PSCA during carcinogenesis of the murine prostate in the transgenic adenocarcinoma of the mouse prostate model showed a markedly increased expression in areas of neoplasia. The transgenic adenocarcinoma of the mouse prostate model may represent a valuable model for the study of PSCA as a potential target for immunotherapy of prostate cancer, despite potential differences in the pattern of expression between mice and humans.