Serum prostate specific antigen (PSA) is elevated beyond the arbitrary cut-off point of 4.0 ng/ml in the majority of patients with prostate cancer (PCa). It may also be greater than 4.0 ng/ml in some benign conditions, including benign prostatic hyperplasia (BPH). Therefore, serum PSA lacks high sensitivity and specificity for PCa. This problem has been partially overcome by calculating several PSA-related indices (such as PSA density, PSA velocity, percent free PSA) and/or evaluating other serum markers (such as human glandular kallikreins and prostate specific membrane antigen). Atypical small acinar proliferation (ASAP) often represents the underdiagnosis of cancer in biopsy material; patients with cancer on the repeat biopsy usually have an elevated serum PSA. Whether the determination of serum PSA can be of help in the identification of patients with isolated prostatic intraepithelial neoplasia (PIN), i.e., long before PCa develops, is still being debated