As acute neonatal UV exposure is a major risk factor of cutaneous melanoma [2, 23, 30], we herein investigated the consequences of loss of epidermal RXRα in melanoma formation and determined its collaborative role with signaling pathways linked to melanoma driver mutations [NRAS (Q61K) and activated Cdk4 (R24C)] for the formation of spontaneous and acute UVB-induced melanomas. Here, CDK4 is linked to melanoma.