In this study, we investigated the correlation between serum DHEA concentrations measured by liquid chromatography-tandem mass spectrometry (LC–MS/MS) in men with PSA levels of < 10 ng/mL prior to an initial prostate biopsy and prostate cancer detection, with the aim of differentiating men with benign prostatic hyperplasia (BPH) or prostate cancer with a Gleason score of ≤ 3 + 4 (≤ GG 2), who have a small risk of progression and candidate for AS, from men with a Gleason score of ≥ 4 + 3 (≥ GG 3). This evidence concerns the gene KLK3 and benign prostatic hyperplasia.