Ductal adenocarcinoma of the prostate, previously referred to as endometrioid cancer, is typically diagnosed on transurethral resection. When treated by radical prostatectomy (RP), it pursues a more aggressive clinical course than usual acinar prostate cancer does. The significance of prostate cancer with ductal features found on needle biopsies from the peripheral zone is unknown. We reviewed 58 prostate needle biopsy cases with ductal adenocarcinoma for which we were able to obtain clinical information. Patients had a mean age of 69 years (range, 50-89 years) and had a wide range of levels of serum prostate-specific antigen (median, 7.9 ng/mL) and clinical stages. Six (10%) had metastases at the time of diagnosis. Cribriform or papillary structures or a mixture of the two patterns were seen in 86% of cases, whereas in the remaining cases, discrete glands composed of tall columnar cells were present. Stromal fibrosis accompanied the ductal carcinoma in 67% of the cases. A coexisting acinar carcinoma component was identified in 48% of the biopsy specimens. On biopsy, the ductal component composed a mean of 82% of the tumor. Of the 20 tumors treated by RP, 63% had extraprostatic spread of tumor and 20% had positive margins. Two (10%) cases showed seminal vesicle invasion, but none had lymph node metastases. The number of positive needle cores correlated with RP margin status (p<0.004) and with likelihood of clinical progression (p<0.02), but not with organ-confined status. Tumor volume calculated on the 11 extensively sampled RPs ranged from 0.15 cm3 to 20.3 mL (mean, 2.8 cm3). Two years after therapy, the actuarial risk of progression was between 34% (RP patients) and 42% (all patients). A shortened average time to progression was observed relative to a previous study group of men with acinar carcinoma. Serum prostate-specific antigen levels correlated with neither RP organ-confined status nor tumor volume. We conclude that prostatic ductal adenocarcinoma seen on needle biopsy implies more advanced cancer with a shortened time to progression.