Prostate-specific antigen (PSA) is a glycoprotein that is produced by the prostate gland, the lining of the urethra, and the bulbourethral gland. Normally, very little PSA is secreted in the blood. Increases in glandular size and tissue damage caused by benign prostatic hypertrophy, prostatitis, or prostate cancer may increase circulating PSA levels. PSA exists in serum in multiple forms: complexed to alpha-1-anti-chymotrypsin (PSA-ACT complex), unbound (free PSA), and enveloped by alpha-2-macroglobulin (not detected by immunoassays). Higher total PSA levels and lower percentages of free PSA are associated with higher risks of prostate cancer. Most prostate cancers are slow growing, so the utility of prostate cancer screening is marginal in most men with a life expectancy of less than 10 years. When total prostate-specific antigen (PSA) concentration is below 2.0 ng/mL, the probability of prostate cancer in asymptomatic men is low, further testing and free PSA may provide little additional information. When total PSA concentration is above 10.0 ng/mL, the probability of cancer is high and prostate biopsy is generally recommended.