A 71-year-old man presented with asymptomatic, MCPyV-positive MCC that progressed through > 5 therapeutic regimens, including surgery, RT, cytotoxic chemotherapy, IT IL-12, an IT toll-like receptor (TLR)-4 agonist, somatostatin analogues, and nivolumab. The gene discussed is TLR4; the disease is Merkel cell skin cancer.