Purpose: The central zone of the prostate gland is a region rarely associated with carcinoma. To our knowledge central zone tumors have not previously been compared to carcinoma originating in the peripheral or transition zone of the prostate gland.Materials and Methods: All 2,010 radical prostatectomy cases seen at our institution from October 1998 to December 2006 were reviewed to identify tumor zonal origin. Central zone carcinoma was characterized and compared with tumors of other zones.Results: Zonal origin was determined in a total of 2,494 tumors in 1,703 cases. Of the tumors 63 (2.5%) were of central zone origin with 59 of the. 63 representing the index or main tumor. Comparative analysis of a defined subset of 726 cases showed that central zone cancers were significantly more aggressive than peripheral or transition zone cancers with a far greater risk of extracapsular extension, seminal vesicle invasion and positive surgical margins. Escape from the gland was often via the ejaculatory ducts and seminal vesicles. Kaplan-Meier analysis confirmed that the probability of post-prostatectomy biochemical failure was double that of tumors of the other zones with a far more rapid rate of failure. Multivariate Cox regression analysis identified Gleason grade, positive margins, extracapsular extension, tumor volume and preoperative serum prostate specific antigen as the major contributors to this poor prognosis, rather than specific zonal origin.Conclusions: To our knowledge this study provides the first characterization and comparative analysis of central zone carcinoma, identifying these tumors as a rare but highly aggressive form of prostate carcinoma with a distinct route of spread from the gland that contrasts with tumors of other zones. Preoperative identification is currently hampered by the avoidance of biopsy targeting the central zone. However, if recognized preoperatively, aggressive intervention may possibly improve the currently bleak outlook.