Although chromosome 6q instability and loss of heterozygosity (LOH) have been reported in melanoma [64] and associated with low SOD2 expression during the process of SV40 fibroblast transformation [80], SOD2’s role as a tumor suppressor is most commonly associated with SOD2 expression decreases through SOD2 epigenetic regulation or inhibition of tumor associated signaling that affect the basal and enhancer transcriptional machinery. This evidence concerns the gene SOD2 and melanoma.