Basal cell proliferation is a common finding in a benign hyperplastic prostate gland. Occasionally, basal cell hyperplasia is so florid that it can be mistaken for prostatic adenocarcinoma. We characterized histological, ultrastructural, and immunohistochemical features of florid basal cell hyperplasia from transurethral resections (n = 11) and prostatectomy specimens (n = 4). Fifteen cases of prostatic adenocarcinoma were used as comparison. Intraluminal calcification was present in 40% of florid basal cell hyperplasia cases (6 of 15) and a unique finding of intracytoplasmic hyaline globules was detected in 53.3% of florid basal cell hyperplasia cases (8 of 15). Ultrastructural analysis revealed luminal calcification and intracytoplasmic electron-dense globules in foci of basal cell hyperplasia. Crystalloids, a frequent finding in low-grade prostate cancer, were absent in all 15 cases of florid basal cell hyperplasia. By immunohistochemistry, the basal cell-specific 34betaE12 and p63 as well as glutathione-s-transferase pi were positive in all basal cell hyperplasia cases but negative in all prostatic adenocarcinomas. These distinguishing features of florid basal cell hyperplasia are helpful in differential diagnosis from prostatic adenocarcinoma. Cytokeratins 8 and 18 were both positive in basal cells, benign secretory cells, and carcinoma cells, failing to be of discrimatory value. Immunostaining for alpha-methylacyl-coenzyme racemase, a new prostate cancer marker, was negative in hyperplastic basal cells but detected a distinct minor benign cell population in basal cell hyperplasia of possible neuroendocrine origin.