Previous studies of prostatic duct adenocarcinoma have reported a poor prognosis, but they included few patients treated by radical prostatectomy. The authors studied 15 cases treated with radical prostatectomy to define more completely their pathologic features and determine the clinical outcome in these surgically treated patients. The study included morphometry and DNA image analysis using the CAS-200 system. The most common presentation was urinary outlet obstruction (n = 9), and most patients were clinical Stage B with palpable prostatic lesions (n = 12). Compared with acinar cancers of similar clinical stage, duct cancers were large (tumor volume, 8.4 +/- 10.0 cc) and occupied a large portion of the gland (23 +/- 21%). Duct cancers were in an advanced final pathologic stage with 93% having capsular penetration, 47% positive margins, 40% seminal vesicle invasion, and 27% positive pelvic lymph nodes. The DNA analysis on cells disaggregated from paraffin revealed that 54% of cases were diploid, 15% tetraploid, 8% aneuploid, and 23% tetraploid/aneuploid. On clinical follow-up, eight patients had no evidence of tumor at intervals ranging from 1 to 28 months, and seven patients (47%) had persistent tumor at intervals of 3 to 18 months. This study demonstrates that duct cancers are in an advanced pathologic stage by the time of presentation and have a much higher short-term failure rate after radical prostatectomy compared with acinar cancers.