Background: Although PSA unquestionably impacted the early detection of prostate cancer, specificity of the test remains a problem. This problem is especially evident in PSA range 4–10 ng/ml that is often called ‘‘gray zone’’. Numerous studies have shown that 25–30% of men have prostate cancer in this PSA range. Objective: This study was conducted to evaluate the role of cPSA in diagnosis of cancer prostate and compare it with other tests including PSA, PSA derivatives and volume based parameters using different ranges of PSA starting from 2.5-10, 4-10 and 2.5-20 ng/ml. The diagnostic validity, sensitivity, specificity and cut-off values were evaluated by Receiver Operating Characteristic (ROC) curve analysis. Subjects and Methods: PSA and its derivatives including complexed PSA (cPSA), free PSA (fPSA), total PSA (tPSA), free/total PSA (f/tPSA), complex/total PSA (c/tPSA), PSA density (PSAD), complex PSA density (cPSAD), transitional zone PSA density (TZ PSAD), transitional zone complex PSA density (TZ cPSAD) were tested in patients with different ranges ( 2.5-10, 4-10 and 2.5-20 ng/ml) . The diagnostic validity, sensitivity, specificity and cut-off values were evaluated by Receiver Operating Characteristic (ROC) curve analysis. Results: In PSA range of 2.5-10 ng/ml, 4-10 ng/ml and 2.5-20 ng/ml, the AUC was highest for cPSA followed by cPSAD, then f/tPSA and least for PSA. At sensitivity 90%, the cutoffs of cPSA at different PSA ranges (2.5-10 ng/ml, 4-10 ng/ml and 2.5-20 ng/ml) were 2.83 ng/ml, 3.1 ng/ml and 2.83 ng/ml leading to a specificity of 29.9%, 24.2% and 24.4%, respectively. As regards TZ volumes, our results demonstrated that AUC values for cPSAD steadily increased as the TZ volumes decreased and in order to enhance the diagnostic performance of cPSA, cPSAD could be used in prostates with low transition zone volumes (with total prostatic volume < 45 ml). Whereas TZ cPSAD might be taken into consideration in prostates with larger transi¬tion zone volumes (with total prostatic volume >45 ml). Conclusion: Measurement of cPSA as a single test leads to improvement both in the sensitivity and specificity of the assay and in the same time it has an economic advantage due to use of this marker as a single analyte instead of two or more. Also, it is possible to avoid the variability observed when different manufacturers assays are used in measurement of more than one analyte. Besides, there is little uniformity and standardization among the numerous total PSA and free PSA assays available in the market. Also cPSA is more stable and it can be used easily without degradation than the other PSA isoforms till now. In addition, cPSA is exceptionally stable in specimens stored for long durations (as long as 18 months) when compared to the other PSA derivatives that show a great instability and need special precautions to preserve and handle. Further studies should be performed in a large scale population to study the diagnostic performance of volume related cPSA assays.