About 43% of men with low Gleason grade prostate cancer (PCa) at biopsy will be finally diagnosed with high-grade PCa at radical prostatectomy (RP). Gleason sum at RP is a good indicator of biochemical recurrence and poor clinical outcome. Therefore, there is a need to improve clinical evaluation of PCa aggressiveness in order to choice appropriate treatment. To this aim an easy-available tool is represented by circulating biomarkers. Among these, the best candidates are some molecules involved in PCa pathogenesis such as IGFBP-2 and IGFBP-3, IL-6, and its soluble receptor (SIL-6R).