DNA methylation, along with covalent histone posttranslational modifications, chromatin remodelling and non-coding RNAmediated gene interference, represents an important mechanism in the integrated apparatus of epigenetic regulation. In addition to playing a role in several physiological processes, epigenetic mechanisms have been described as key factors in modifying the accessibility of DNA to transcription factors and, therefore, in altering the gene expression patterns of several cancer types. Given the existence of relatively simple approaches that require even minute amounts of tumour DNA, the best factor described involved in melanoma epigenetics is DNA methylation, a covalent modification of mainly cytosines. The DNA hypermethylation is usually strictly localised to the transcriptionally active gene regions and promoters and directly inhibits gene expression. In the field of malignant melanoma epigenetics, there are substantial amounts of data available regarding gene silencing associated with the localised CpG hypermethylation of specific gene promoters. However, most of the provided data are derived from cell lines or were generated using single-gene approaches. Despite the fact that some groups have attempted to conduct array-based experiments, to date, there are no methylation markers of the diverse melanoma subgroups based on a stratified analysis with sufficient statistical power. Therefore, having chosen a powerful and high-throughput bead array technology, we performed array-based experiments to define the methylation pattern of 1,505 gene promoters. Previous studies have provided irrefutable proof of the reproducibility of this approach. The simultaneous detection of transposonal demethylation and promoter methylation changes should provide valuable information regarding the molecular mechanisms potentially responsible for the aggressive phenotype of malignant melanoma. Recently, it has become widely accepted that Knudson’s two-hit hypothesis is often confirmed through a combination of differing types of genomic alterations, which prompted us to investigate whether methylation patterns are associated with other types of somatic alterations, such as the most frequent mutations and DNA copy number alterations. Notable previous investigations demonstrated the prognostic relevance of CN aberrations. Therefore, we also highlighted the cis-and trans-acting CN alterations of gene expression in malignant melanoma. Moreover, we and others have demonstrated the association of BRAF and NRAS mutations with CN alterations using BAC arrays, suggesting a central role of BRAF mutations in gene copy number changes. Additionally, a single group reported that the impact of BRAF signalling on gene methylation is widespread. Despite the promising initial results, to our knowledge, no direct, array-based experiments have been performed in an integrative approach in a wide variety of primary melanomas.