The recognition of the role played by TRAIL-mediated apoptosis in the process of immune surveillance counteracting tumor formation has led to the development and clinical employment of TRAIL-receptors targeting compounds as anticancer therapy; at this time, monoclonal antibodies targeting TRAIL-R1 (e.g. mapatumumab [17]) or TRAIL-R2 (e.g. tigatuzumab [18]), or recombinant forms of human TRAIL [19], are undergoing extensive clinical investigation. This evidence concerns the gene TNFRSF10B and neoplasm.