Prostatic urothelial-type adenocarcinoma arises through a process of glandular metaplasia of the prostatic urethral urothelium and subsequent in situ adenocarcinoma sometimes associated with villous adenoma. These prostatic adenocarcinomas are analogous to nonurachal adenocarcinomas arising in the bladder from cystitis glandularis. Only 2 cases of urothelial-type adenocarcinoma from an institution other than our own have been previously described. The distinction between adenocarcinoma from another organ secondarily involving the prostate, usual adenocarcinoma of the prostate, and prostatic urothelial-type adenocarcinoma can present a significant diagnostic challenge and has significant therapeutic implications. Fifteen cases of prostatic urothelial-type adenocarcinoma were retrieved from the consult files of one of the authors. Mean patient age at diagnosis was 72 years (range 58 to 93 y). All men had negative colonoscopies, clinically excluding a colonic primary. Bladder primaries were ruled out clinically or pathologically in radical resection specimens. Follow-up was available on all men with a mean of 50.3 months (range 2 to 161 mo). All men presented with urinary obstruction symptoms with 3 (20%) also having mucusuria and 2 (13.3%) also having hematuria. Four men (26.7%) developed metastatic disease and 8 (53.3%) died of disease. In 8/15 (53%) cases, glandular metaplasia of the prostatic urethra and contiguous transition to adenocarcinoma were identified. Multiple histologic patterns were observed including dissection of the stroma by mucin pools 15/15 (100%), villous features 7/15 (47%), necrosis 2/15 (13.3%), signet ring cells 3/15 (20%), perineural invasion 1/15 (6.7%), focal squamous differentiation 1/15 (6.7%), and a granulomatous inflammatory response 1/15 (6.7%). Immunohistochemical stains were negative for prostate specific antigen, prostate specific acid phosphatase, CDX2, and beta-catenin in all cases. Stains were positive for high molecular weight cytokeratin in 12/12 cases (100%), and CK7 and CK20 in 10/12 cases (83.3%). Prostatic urothelial-type adenocarcinoma is a rare aggressive cancer arising in the prostate. The differential diagnosis includes conventional prostatic mucinous adenocarcinoma and secondary infiltration from a colonic or bladder adenocarcinoma. Immunohistochemistry for prostate specific antigen, prostate specific acid phosphatase, and high molecular weight cytokeratin along with morphology can help rule out conventional prostate carcinoma. beta-catenin, CDX2, and clinical studies are needed to rule out colonic adenocarcinoma. As prostatic urothelial-type adenocarcinoma is entirely analogous to bladder adenocarcinoma in both, its morphology and immunophenotype, only clinical studies or in some cases pathologic examination of the cystoprostatectomy specimen can exclude infiltration from a primary bladder adenocarcinoma.