Because of the widespread use of keratin 34 beta E-12 to assist in the distinction between benign acini and malignant glands, the lack of immunoreactivity of benign prostatic acini are important issues. We studied midprostate whole-mount sections from 21 low-volume adenocarcinoma radical prostatectomy specimens with keratin 34 beta E-12. We marked out benign 0.25-cm2 areas in the peripheral and transition zones and counted the number of small acini immunoreactive with keratin 34 beta E-12 to a total of 50 acini within each area. Small benign acini from nonatrophic peripheral zone lobules of 3 prostate specimens were examined by electron microscopy. The median number of immunoreactive acini in each region was 49. The nonreactive acini were always the most peripheral acini in a lobule, a small cluster of outpouched acini furthest from a large duct, or the terminal end of a large duct. More proximal acini had a discontinuous pattern of immunoreactivity. Electron microscopy showed occasional acini with luminal cells abutting the basement membrane, without the interposition of basal cell cytoplasm, and other acini with extremely attenuated basal cell cytoplasmic processes containing sparse bundles of intermediate filaments. The basal cell layer becomes attenuated toward the periphery of some lobules and duct outpouchings, producing nonreactive acini adjacent to discontinuously reactive acini.