“Over-treatment,” through the detection of non-life-threatening tumors [7], especially in the so-called gray zone (serum PSA between 4–10 ng/mL), represents yet another dilemma, as it is difficult to discriminate between patients with PCa and those with benign prostatic hyperplasia (BPH) or between those patients suffering from prostatitis and the results of urethral manipulation, which can also increase PSA levels [8]. This evidence concerns the gene KLK3 and medical procedure.