Prostate specific antigen (PSA) is the most beneficial tumor marker for prostate cancer, Since the introduction of PSA assays over a decade ago, their impact on the early detection of prostate cancer has been evident in prostate cancer incidence rates. Although the considerable number of commercial assays may differ as a result of assay design and calibration, PSA is effective for detection of cancer and recurrence, and for cancer staging and monitoring. In serum, PSA is present in the free, unbound form as well as complexed to protease inhibitors. Use of the molecular forms of PSA is now under investigation as a method to increase the clinical utility of PSA for the detection of prostate cancer. A greater percentage of PSA is bound to alpha(1)-antichymotrypsin (ACT) in prostate cancer patients than in patients with benign prostate disease. In the diagnostic gray zone (4-10 mu g/L) where PSA concentrations overlap for cancer and non-cancer, unnecessary biopsies may be eliminated with the determination of percent free PSA, Initial work has focused on free PSA assays due to technical issues in the development of assays for the complexed forms of PSA, Although complexed PSA assays have recently been developed, further research is needed to define the role of complexed PSA as a tumor marker for prostate cancer.