We studied 33 cases with an initial needle biopsy of the prostate that showed only high-grade prostatic intraepithelial neoplasia (PIN 2-3), for which follow-up biopsies were available. Twenty-four men (73%) were shown to have adenocarcinoma either on a simultaneous (14 patients) or subsequent (10 patients) biopsy. The grade of PIN (grade 2 v 3), rectal examination findings, and transrectal ultrasound results proved not to be significantly different in patients with proven adenocarcinoma compared with those without proven carcinoma. In contrast, serum prostate-specific antigen (PSA) concentrations were elevated in 90% of patients with carcinoma compared with only 50% of those with a benign follow-up biopsy. Persistent elevation of serum PSA concentration was seen in only one of three patients with serial PSA measurements and a benign follow-up biopsy. Notably, all patients with carcinoma for whom we had serial measurements of serum PSA levels had persistent elevation. The finding of high-grade PIN on needle biopsy often represents a sampling problem with carcinoma nearby. Consequently, the finding of high-grade PIN on needle biopsy merits vigorous follow-up, including rebiopsy. In particular, patients with increased serum PSA appear to be at greater risk of harboring prostatic adenocarcinoma. However, a significant number of patients with high-grade PIN on initial biopsy may not have evidence of carcinoma on repeat biopsy. Thus, radical prostatectomy or radiotherapy for PIN is not warranted.