We studied the relationships between the outcome in the last follow-up prostate biopsy specimen and serum prostate-specific antigen (PSA), prostatic intraepithelial neoplasia (PIN), and atypical small acinar proliferations (ASAPs) at the occasion of the initial biopsy in 244 cases in which the initial specimen was negative for tumor and at least 1 follow-up biopsy was done. PSA levels and ASAPs were significantly associated with cancer in the follow-up biopsy specimen (<P < .005; logistic regression analysis); however, the presence of PIN in the initial biopsy specimen did not relate to cancer in the follow-up specimen (P > .1). Thus, the probability that a follow-up biopsy demonstrates cancer depends on PSA and ASAPs, and even when ASAPs are present, serum PSA exerts an influence. For example, low PSA values, 5 ng/mL (5 mug/L) or less, are associated with low probabilities of a positive follow-up biopsy result, even when ASAPs were present in the first biopsy specimen. For higher PSA values, the presence of ASAPs dramatically increases the probability of a positive follow-up biopsy result compared with cases with no atypia or PIN in the first biopsy specimen.