The key pathogenetic role of HMGB1 in cutaneous melanoma has been revised based on the emerging body of work in recent years, emphasizing its involvement in promoting neoangiogenesis, pro‐tumor immunity (via accumulation of IL‐10‐producing M2 macrophages) as well as production of pro‐inflammatory cytokines IL‐23 and IL‐17 and suppression of cytotoxic T lymphocytes (CTLs) activity (via the RAGE/HMGB1 axis), thus enhancing tumor growth alongside the metastatic phenotype. This evidence concerns the gene HMGB1 and neoplasm.