Currently there are two hypothesized pathways in MCC pathogenesis: (1) clonal integration of the Merkel cell polyomavirus (MCPyV) into the dermal-located precursor cells, and (2) ultraviolet irradiation of the intraepidermal stem cells or Merkel cells, which is characterized by a UV-mutational signature: frequent C > T/A > G and CC > TT/AA > GG transitions and recurrent tumor protein 53 (TP53) and RB transcriptional corepressor 1 (RB1) mutations [9,10]. This evidence concerns the gene RB1 and Merkel cell skin cancer.