MCPyV-negative cases belong to the group of MCC with the greatest amount of molecular alteration [2,3]; indeed, MCPyV-negative MCC has been associated to the UV radiation mutational signature, namely, a predominance of cytosine to thymidine transition at DNA dipyrimidine sites, and to a tumor mutational burden 25–90-fold higher than the MCPyV-positive counterpart [2,42,43,44]; thus, the nuclear TRK expression observed in some MCC cases may be due to an aberrant protein product of mutated NTRK genes. The gene discussed is NTRK1; the disease is Merkel cell skin cancer.