To better represent the Gleason score of radical prostatectomy, the International Society of Urologic Pathologists Consensus Committee recommends assigning individual Gleason scores to prostate cancer cores submitted in separate containers and/or multiple cores in the same container with site identifiers. However, scenarios where multiple cores are submitted in the same container without site identifiers or labeled "left/right" are common. To assess this scenario, we analyzed 110 extended biopsies containing different Gleason scores with corresponding radical prostatectomy for clinically significant grade differences. Because cores are individually labeled and submitted at our institution, we simulated a scenario of multiple intact cores with different Gleason scores in the same container(s) by analyzing as if submitted in containers labeled "left/right." For each biopsy, a Global (all positive cores averaged as 1 long positive core), Worst, and Largest tumor volume Gleason score was determined and compared with grade of radical prostatectomy using kappa statistics. Biopsies containing core(s) with 3+4 and other core(s) 3+3 were excluded because in this situation, both Global and Worst Gleason score will be always 3+4. The following scenarios were considered clinically significant upgrading: biopsy Gleason score 6 / 3+4 to radical prostatectomy 4+3; biopsy 7 to radical prostatectomy 8-10; biopsy 7 to radical prostatectomy 7 with tertiary Gleason pattern 5. Overall, 51 cases met inclusion criteria. Biopsy Worst Gleason score had the best correlation with radical prostatectomy (kappa agreement of 0.37). Clinically significant upgrading at radical prostatectomy was least with Worst (4%) and highest with Global Gleason score (37%). Upgrading and downgrading were noted in 14% and 8%, respectively, of 59 cases containing core(s) with a Gleason score of 3+4 and other core(s) 3+3, suggesting that any amount of higher Gleason pattern should be recorded. When multiple intact cores are submitted in the same container without specific identifiers, individual cores with cancer should be graded and/or the Worst Gleason score should be recorded.