Many of the difficulties in understanding diseases of the prostate have arisen through poor understanding of the anatomy of the prostate. The recent description of histologically separate zones in the prostate has been an important advance, allowing evaluation of separate cancers arising in the transition and peripheral zones of the prostate. While the majority of cancers sampled at transurethral resection of the prostate (TURP) are of transition zone origin, most of these prostates contain separate cancers in the peripheral zone. The peripheral zone cancers have a higher grade-to-volume ratio and are more frequently associated with histological features of progression (extracapsular extension, seminal vesicle invasion) than transition zone cancers. Furthermore, peripheral zone cancers are frequently associated with prostatic intraepithelial neoplasia, in contrast to transition zone cancers. These findings suggest a greater biological activity for cancers arising in the peripheral zone. The majority of cancers detected by digital rectal examination are of peripheral zone origin. While associated transition zone cancers are less frequently present than in TURP sampled prostates, a similarly high association of peripheral zone cancers with histological indicators of biological activity is seen. DNA ploidy analysis of separate foci in radical prostatectomy specimens confirms a significantly higher rate of non-diploidy in cancers of peripheral zone origin, some of very small volume, which further suggests a greater biological activity compared to transition zone cancers.