Prior studies of radical prostatectomies have reported a small percentage of men with biochemical progression after radical prostatectomy showing organ-confined, Gleason Score 6. One might predict that this should virtually never occur. We identified 2551 (1983-2005) radical prostatectomies coded by the urologists at our institution as pathologically organ-confined, Gleason score 6 cancer with more than 1 year of follow-up. We re-examined histopathogically the serially sectioned and completely embedded radical prostatectomy specimens of 38 men who developed biochemical recurrence defined as a single prostate-specific antigen level of 0.2 ng/mL or greater. In 27 (71%) of 38 of cases, pathology re-review showed higher grade or stage than coded by the urologists. These included 10 cases of organ-confined with Gleason pattern 4 as either the primary or secondary pattern; 9 cases of organ-confined, Gleason score 6 with tertiary pattern 4 (in 4 cases, tertiary pattern 4 was described in the initial pathology report); 5 cases of Gleason score 7 plus extraprostatic extension; 1 case of Gleason score 6 with focal extraprostatic extension; and 2 cases with positive margins due to intraprostatic incision (listed in the initial pathology report). The remaining 11 cases were true organ-confined, Gleason score 6 tumors, but none of the patients developed systemic disease. Most prior reports of organ-confined, Gleason score 6 with progression are undergraded (upgrading with revision of Gleason system), understaged (difficulty recognizing focal extraprostatic extension), or suffer from situations with ambiguous staging (intraprostatic incision) or grading (tertiary pattern 4 or 2 + 4 = 6). Even for the rare true organ-confined, Gleason score 6 (no pattern 4) tumor with supposed biochemical progression, some may be false-positive progression based on low post-radical prostatectomy prostate-specific antigen levels and minute tumors that seem highly improbable to progress. With accurate pathologic evaluation, men with organ-confined, Gleason score 6 (no pattern 4) prostate cancer can be told that their risk of progression is very rare (0.4%).