PURPOSE: The Gleason grading system in reporting prostate cancer accounts for the primary and secondary Gleason pattern. The clinical significance of a higher tertiary (third most prevalent) grade is largely unrecognized. MATERIALS AND METHODS: Radical prostatectomy specimens from 300 patients with Gleason score 7 (3 + 4 or 4 + 3) prostate cancer were pathologically reexamined for the presence of a tertiary grade 5 pattern as well as the association with pathological stage and biochemical recurrence-free survival. RESULTS: A total of 214 patients met study inclusion criteria. Patients with Gleason score 7 and tertiary grade 5 cancer had significantly higher pathological stage disease than patients with Gleason score 7 without tertiary grade 5 cancer (p <0.001). Gleason score 7 + tertiary pattern 5 tumors were significantly associated with adverse pathological features such as seminal vesicle invasion, extraprostatic extension and lymphovascular invasion compared to Gleason score 7 tumors (p <0.05). The relative effects of a tertiary grade 5 component on all pathological parameters analyzed was greater for Gleason score 7 tumors with a lower primary Gleason pattern 3 vs a higher primary Gleason pattern 4. Patients with Gleason score 7 + tertiary pattern 5 tumors had significantly decreased biochemical recurrence-free survival (54 months) compared to patients with Gleason score 7 tumors (121 months) (p = 0.0005). Preoperative prostate specific antigen, lymphovascular invasion and positive surgical margin status were shown to be independent predictors of prostate specific antigen recurrence on multivariate analysis. CONCLUSIONS: Small percentages of tertiary grade 5 patterns in Gleason score 7 radical prostatectomy specimens are associated with aggressive pathological features predictive of advanced pathological stage and biochemical recurrence-free survival.