For over two decades, several efforts have been made to define and molecularly characterize the frame of neuroendocrine (NE) prostate cancer (NEPC) presenting with distinct clinical features, different from the classic prostatic adenocarcinoma, including frequent visceral metastases, lytic bone involvement, relative low serum prostate-specific antigen (PSA) concentration, resistance to androgen ablation, and high response rate to platinum-based chemotherapy (1). This evidence concerns the gene KLK3 and prostate cancer.