In 46 radical prostatectomy specimens, carcinoma volume and Gleason histologic grade were compared among 21 cancers containing Grade 3 cribriform areas and 25 noncribriform carcinomas. All cribriform cancers but only 44% of the noncribriform cancers were larger than 1.7 ml. Grade 4-5 areas were present in 86% of cribriform cancers and 36% of noncribriform cancers. All 17 cancers larger than 4.0 ml contained Grade 4-5 areas, and 15 of these showed cribriform areas. By contrast, noncribriform Grade 3 areas were found in 45 of 46 carcinomas. In most cases, cribriform carcinoma was predominantly intraductal; cell masses either followed normal duct contours or showed a basal cell layer by routine microscopic study or by immunohistochemical staining for basal cell-specific keratin. Seven cases showed primary origin of cribriform carcinoma within ducts by evolution from intraductal dysplasia, a presumptive premalignant lesion. It was proposed that cribriform carcinoma is equivalent to intraductal Grade 4 cancer, and that many Grade 4 prostate cancers may evolve directly from an identifiable intraductal precursor.