It has been suggested that poorly differentiated areas in prostatic carcinoma evolve from more well differentiated cancer with time and increasing tumor volume. However, the association of high grade tumor with increasing tumor volume may merely reflect a growth advantage of the high grade tumor, whereby most high grade tumors would be large by the time they were clinically detected. Prior reports analyzing the relationship of tumor volume and grade suffer from studying fairly advanced tumors in which the relationship of tumor volume and grade at inception of prostate cancer could not be addressed. We evaluated 720 individual tumor foci in 153 radical prostatectomy specimens removed for early prostate cancer detected by screening techniques. Although tumor volume was related to grade, the correlation was weak (r = 0.254). Of 13 peripherally located high grade tumors (Gleason score 8 to 10) 6 (46%) were less than 1 cc. Of 106 peripheral tumors with some Gleason pattern 4 or 5 component 48 (45%) were less than 1 cc. These small high grade tumors were frequently associated with high grade prostatic intraepithelial neoplasia. Small high grade cancers were uncommon within the transition zone, where there exists a greater tendency for large low grade cancers to arise. In this radical prostatectomy series of nonpalpable prostate cancer 9% of the prostates contained tumor foci that were predominantly Gleason pattern 4 or 5 and that measured 1 cc or less. Based on these findings, if some patients with low to intermediate grade cancer are to be followed expectantly, they should undergo widespread sampling of the prostate to enhance the detection of multifocal small high grade disease. The finding of a large proportion of low volume, high grade carcinoma reveals that prostate cancer has the potential to be high grade early in its course and need not arise from low grade carcinoma that has evolved with time and volume.