Objectives: The stage and grade shift of currently diagnosed prostate cancer has led to a diminished prognostic power of the Gleason score system. We investigated the predictive value of the amount of high-grade cancer (Gleason growth patterns 4/5) in the biopsy for prostate-specific antigen (PSA) and clinical relapse after radical prostatectomy. Methods: PSA-tested participants (N = 281) of the European Randomized Study of Screening for Prostate Cancer (ERSPC) who underwent radical prostatectomy were analyzed. Besides clinical features, and serum-PSA, histopathologic features as determined in the diagnostic biopsy and matching radical prostatectomy specimen were related to patient outcome. Results: At a median follow-up of 7 yr, 39 (13.9%), 24 (8.5%), and 12 (4.3%) patients had PSA ≥0.1 ng/ml, PSA ≥1.0 ng/ml, and clinical relapse after radical prostatectomy, respectively. Using Cox proportional hazards, PSA level (p = 0.002), length of tumour (p = 0.040), and length of high-grade cancer (p = 0.006) in the biopsy, but not Gleason score, were independent prognostic factors for biochemical relapse (PSA ≥0.1 ng/ml) when assessed as continuous variables. In radical prostatectomies, the proportion of high-grade cancer (p < 0.001) was most predictive of relapse (PSA ≥0.1 ng/ml). For PSA ≥1.0 ng/ml and clinical relapse, the amount of high-grade cancer, both in the biopsy specimen (p = 0.016 and p = 0.004, respectively) and radical prostatectomy specimen (p = 0.002 and p = 0.005, respectively), but not Gleason score, was an independent predictor. Conclusions: In biopsy and radical prostatectomy specimens of surgically treated prostate cancer, the amount of high-grade cancer is superior to the Gleason grading system in predicting patient outcome. We propose that, in addition to the Gleason score, the amount of Gleason growth patterns 4/5 in the biopsy (whether absolute length or proportion) should be mentioned in the pathology report.