It is unknown whether ductal adenocarcinomas are more aggressive when matched for Gleason score (assigning the ductal component as Gleason pattern 4). Moreover, little is known whether a certain percentage of the ductal component is needed to account for its more aggressive behavior. Of 18,552 radical prostatectomies performed from 1995 to 2008, 93 cases with a ductal adenocarcinoma component were identified. Cases were classified based on their ductal/acinar ratio (<10%; ≥10% and <50%; ≥50%). There was no difference in the distribution of Gleason score 3+4=7 versus 4+3=7 between ductal and nonductal tumors, such that cases were combined as Gleason score 7. There was no age, race, and serum prostate-specific antigen difference between patients with and without ductal adenocarcinoma. Cases with ductal adenocarcinoma were less likely to be organ confined (36.6% vs 65.6%) and more likely to show seminal vesicle invasion (SVI) (19.3% vs 5.3%), P<0.0001. There was no difference in lymph node metastases or positive margins between cases with and without ductal features. An increasing percentage of the ductal component correlated with an increased risk of extraprostatic extension (P=0.04) and SVI (P<0.0001). To account for overall different Gleason scores between ductal and nonductal cases, and the effect of differing percentages of ductal features as well, the following analysis was carried out. For Gleason score 7 cases and ≥10% ductal differentiation, cases with ductal features were more likely to have nonfocal extraprostatic extension (64.0%) versus cases without ductal features (34.7%), P=0.002. In this group, there was no statistically significant difference in SVI or lymph node involvement between Gleason score 7 ductal and nonductal tumors. For Gleason score 7 cases with <10% ductal features, there was no difference in pathologic stage versus nonductal cases. There was no difference in pathologic stage between ductal and nonductal cases for Gleason score 8 to 10 cases, regardless of the percentage of the ductal component. This study shows that ductal adenocarcinoma admixed with Gleason pattern 3 is more aggressive than Gleason score 7 acinar cancer, as long as the ductal component is ≥10%. In cases with a very minor ductal component, these differences are lost. In addition, Gleason score 8 to 10 tumors with ductal features are not significantly more aggressive that acinar Gleason score 8 to 10 cancers in which the pure high-grade tumor, regardless of ductal features, determines the behavior.