We examined 238 prostate biopsy cores from 40 sextant biopsies by routine H&E stain to determine the presence of prostatic adenocarcinoma (PCa), perineural invasion (PNI), and nerves. Step sections were immunostained for S-100 protein to confirm the presence of nerves. Nerves were distributed evenly in specimens from apex, mid gland, and base. No significant difference was observed in the number of nerves in these areas. Significantly more nerves were found using the S-100 stain than the H&E stain. There was no significant difference between cancerous and benign specimens. However, there was a significant reduction in the nerve density in cancerous compared with benign specimens. PNI was identified in 3 of 11 PCas. All foci of PNI were identified on H&E stain. The S-100 immunostain detected no additional foci of PNI. Nerves are distributed evenly in standard sextant biopsy specimens from prostatic apex, mid gland, and base. In addition, the specimens with PCa have nerve distribution similar to that of benign specimens, suggesting that finding no PNI may represent true absence of PNI in the specimens. Careful examination of routine H&E-stained specimens is sufficient to detect all important PNI.