Both genetic mutations and UV irradiation (UVR) can predispose individuals to melanoma. Although BRAF^V600E is the most prevalent oncogene in melanoma, the BRAF^V600E mutant is not sufficient to induce tumors in vivo. Mutation at the CDKN2A locus is another melanoma-predisposing event that can disrupt the function of both p16^INK4a and ARF. Numerous studies have focused on the role of p16^INK4a in melanoma, but the involvement of ARF, a well-known p53 activator, is still controversial. Using a transgenic BRAF^V600E mouse model previously generated in our laboratory, we report that loss of ARF is able to enhance spontaneous melanoma formation and cause profound sensitivity to neonatal UVB exposure. Mechanistically, BRAF^V600E and ARF deletion synergize to inhibit nucleotide excision repair by epigenetically repressing XPC and inhibiting the E2F4/DP1 complex. We suggest that the deletion of ARF promotes melanomagenesis not by abrogating p53 activation but by acting in concert with BRAF^V600E to increase the load of DNA damage caused by UVR. Cancer Res; 73(14); 4337–48. ©2013 AACR.