OBJECTIVE Prostatic carcinomas arising in the transition zone (TZ) are thought to differ from the more frequent cancers of the peripheral zone (PZ) with regard to morphology and biologic behavior. It is unclear, however, whether the differences are reflected in genetic alterations. METHODS We assessed numerical aberrations of chromosomes 7, 8, 10, 17, and X with interphase cytogenetics in 10 radical-prostatectomy specimens containing exclusively TZ cancers larger than 0.5 cm.3 and in 10 additional specimens containing both TZ and PZ cancers larger than 0.5 cm.3 each. RESULTS Of the 20 TZ carcinomas, 9 were completely disomic, 5 were at least focally tetrasomic but not aneusomic, and 6 were focally aneusomic. Ploidy correlated well with tumor volume (p = 0.0083), grade (p = 0.0064) and surgical margins (p = 0.0141) but not with preoperative prostate-specific antigen. A strong correlation was observed between the presence of low grade tumor (Gleason grade 4 or 5) and a nondiploid chromosomal status (p = 0.0001). In 10 cases there were also foci of PZ cancer larger than 0.5 cm.3, of which 4 were disomic, 3 were tetrasomic at the most, and 3 were aneusomic. The mean tumor volumes of disomic and aneusomic cancers differed significantly between TZ and PZ carcinomas (p = 0.0336 and 0.0476, respectively). CONCLUSIONS Numerical chromosomal instability parallels tumor progression in TZ carcinomas of the prostate. However, our results indicate that PZ and TZ cancers differ in that the latter can reach larger volumes before histological dedifferentiation and aneusomy occur.