In the present study, a cohort of patients SPMs (n = 20) and MPMs (n = 19), sex-matched, was analyzed with our custom NGS panel that included 32 genes involved in melanoma susceptibility (e.g., CDKN2A, BAP1, POT1) and skin/hair pigmentation (e.g., TYR, TYRP1, OCA2). This evidence concerns the gene CDKN2A and secondary progressive multiple sclerosis.