OBJECTIVE: Compare the capacity of the PSA density (PSAD), Free PSA percentage (%FPSA) and PSA transition zone density (PSATZ) in improving the sensitivity and specificity of the PSA to detect prostate cancer (PCa) in men with a PSA between 4 and 10 ng/mL. MATERIALS AND METHODS: One hundred and forty five men with PSA between 4 and 10 ng/mL were prospectively studied. Blood collection for the total PSA and free PSA was performed as well as transrectal ultra-sound with prostate biopsy and measurement of the total prostate volume (TPV) and transition zone volume (TZV). Patients with initial negative biopsy were followed and the prostate biopsy was repeated in those that presented PSA increase. The capacity of the PSAD, %FPSA and PSADTZ in improving the sensitivity and specificity pf the PSA test to the detection of the PCa was assessed by univariate and multivariate analyses and through the ROC curve. RESULTS: Of the 145 patients, 38 (26.2%) had PCa and in 107 (73.8%) a benign prostate disease was diagnosed. No difference among the PSAD, %FPSA and PSADTZ was found. The multivariate analysis showed that the PSADTZ, %FPSA, TZV and age were those more powerful and highly significant PCa predictors. CONCLUSION:The determination of %FPSA and PSAD can allow a better discrimination between PCa and benign disease that the isolated use of PSA. The combination of PSADTZ, %FPSA, TZV and age promote a high accuracy for PCa detection.