Context.-Use of the International Society of Urological Pathology (ISUP) 2005 modified Gleason score may result in higher scores compared with the classic Gleason scoring system. Objective.-To compare scores derived using the 2 scoring systems. Design.-On-study and for-cause biopsies were centrally reviewed and assigned a classic Gleason score in the Reduction by Dutasteride of prostate Cancer Events trial. Positive biopsies were reviewed by an independent pathologist in a secondary review using the ISUP 2005 modified Gleason score. The independent pathologist also recorded a classic Gleason score. Results.-In total, 1482/1507 (98%) positive biopsy results were independently reviewed. Scores assigned by the 2 pathologists (classic versus modified) agreed in 83% (1230 of 1481) of cases; 99% (1471 of 1481) of cancers were within ±1 of their previous score. Of discordant cases, similar numbers of biopsies were upgraded and downgraded in the secondary review, with minor differences in the score distributions. Interobserver agreement was good, with κ values ranging from 0.62 (95% confidence interval [CI], 0.56-0.67) to 0.70 (95% CI, 0.65-0.76). The overall number of high-grade tumors (Gleason score 8-10; n = 48) remained constant between reviews, with 3 fewer cases in the placebo group (n = 16) and 3 more in the dutasteride group (n = 32) in the secondary review. When comparing the independent pathologist's modified scores versus the classic, 17 of 1481 cancers (1.1%) were upgraded (including 9 of 17 upgrades [53%] to high-grade tumors). Conclusions.-This analysis showed similar score distributions between the classic and modified Gleason scoring systems. The differences seen between the 2 pathologists' scores likely reflect differences in interpretation rather than the scoring system chosen.