To date, only two studies compared the efficacy of systemic immune checkpoint inhibitors in NM versus SSM patients and demonstrated contradictory results: Lattanzi et al. observed no difference in survival outcomes of NM versus SSM patients treated with immunotherapy (anti-PD-1 n = 29, anti-CTLA-4 n = 119), while Pala et al. displayed an improved survival of NM patients treated with immunotherapy compared with SSM patients (anti-PD-1 n = 35, anti PD-1/anti-CLTA-4 n = 7) [16,17]. This evidence concerns the gene CTLA4 and superficial spreading melanoma.