Cases of Merkel cell carcinoma have become increasingly more common in the last two decades, and its incidence has been predicted to climb further. Immunosenescence might explain in part the higher Merkel cell carcinoma prevalence in seniors aged 70 and older. This cancer might also be more aggressive in immunocompromised patients. In a subset of immunocompromised Merkel cell carcinoma patients, we identified significant lymphopenia and a more advanced disease stage compared with their immunocompetent counterparts. Time to death in this cohort was much shorter than in immunocompetent subjects, and their likelihood of death from Merkel cell carcinoma was five times higher. Avelumab approval in 2017 represents an important step forward in the therapy of Merkel cell carcinoma. Hopefully, PD1/PDL1 inhibitors will improve survival in immunocompromised Merkel cell carcinoma hosts, traditionally linked with inferior clinical outcomes.