AIMS: To determine prostate-specific membrane antigen (PSMA) expression in normal tissues and in 3161 benign and malignant tumours and subsequently to define its sensitivity and specificity in prostatic adenocarcinoma (PaC). METHODS AND RESULTS: Multiple tissue microarray sections were stained with a monoclonal antibody to PSMA. PaC was positive in 93/141 cases (66.0%) with various staining patterns including cytoplasmic, apical, apical/cytoplasmic and cytoplasmic with membranous accentuation. Of 2174 various tumour types, 154 expressed PSMA, including 59/346 (17.0%) urothelial carcinomas of the bladder (UBC). In those tumours, the staining pattern was always cytoplasmic. All 846 benign tumours were negative for PSMA. The sensitivity and specificity of PSMA in distinguishing PaC from any other type of malignancy is 65.9% and 94.5%, respectively. Furthermore, its sensitivity and specificity in differentiating PaC from urothelial cancer is 65.9% and 82.9%, respectively. CONCLUSIONS: Despite its expression by subsets of various types of malignancies, PSMA is still considered to be fairly sensitive and highly specific for PaC.