Transition to invasive melanoma “inherits” driver mutations from the primary, early, cutaneous lesion(s) (e.g., BRAF and TERT) and “acquires” additional, critical, alterations, detrimentally deregulating cell-cycle control (e.g., CDKN2A; encodes p16INK4A and p14ARF), cell identity (e.g., ARID1A or/and ARID2), cell growth (e.g., PTEN), and apoptosis (e.g., TP53) programs [7,12,13,14]. This evidence concerns the gene TP53 and melanoma.