Thirteen cases of prostatic adenocarcinoma with endometrioid features were reviewed. The patients were older men (49-81 years) presenting with symptoms of hematuria and urinary obstruction. Each of the tumors displayed exophytic growth into the prostatic urethra, with involvement of the verumontanum. The urethral orifices of the large (primary) prostatic ducts were uniformly involved, and coexistent invasive (acinar) adenocarcinoma was identified in 10 cases (77%). The tumors exhibited a complex glandular pattern strikingly similar to uterine endometrial carcinoma, with prominent papillary formation in six cases. All cases demonstrated intense cytoplasmic immunoreactivity for prostatic acid phosphatase and prostate-specific antigen in at least part of the tumor. Focal staining for carcinoembryonic antigen was seen in three cases. Five tumors examined ultrastructurally demonstrated typical features of prostatic adenocarcinoma. Follow-up information was available on all 13 patients (6-83 months). Seven patients died of metastatic tumor (9-70 months after diagnosis), and the other six patients exhibited recurrent local or metastatic tumor. The sites of metastases were identical to those seen with invasive "acinar" prostatic adenocarcinoma, including pelvic lymph nodes, bones, and lungs. Crude 5-year survival was 15%, with a mean survival of 37 months. Adjuvant therapy provided palliative relief for many patients, but did not appear to influence survival. These findings indicate that endometrioid carcinoma is a histologically distinct variant of prostatic adenocarcinoma, with a more aggressive clinical behavior than previously thought.