Melanoma is a serious form of skin cancer: New Zealand has among the highest rates in the world (50 per 100,000). Although survival has improved due to advances in therapies, metastasis is still a major cause of mortality in melanoma patients. Metastasis is very likely to be related to tumour microenvironment, e.g. hypoxia, but a better understanding of the underlying mechanisms is required. Previously, we, and others, demonstrated two main subgroups of gene expression, which correlated with non-invasive and invasive behavioral characteristics of melanoma cell lines. In the present study we hypothesized that differential DNA methylation could be associated with invasive and non-invasive melanomas. We carried out genome-wide DNA methylation analysis using reduced representation bisulphite sequencing (RRBS). A total of 39 differentially methylated fragments (DMFs) were identified in invasive versus non-invasive cell lines, with 20 DMFs being hypermethylated and 19 DMFs hypomethylated. Integrated analysis of DNA methylation and RNA sequencing (RNA-Seq) was carried out on these cell lines to identify possible relationships between DNA methylation and gene expression, resulting in a total of 17 common differentially expressed genes associated with differential DNA methylation. Further analyses of these data are on-going, including RNA-Seq analysis of 70+ melanoma cell lines, including 8/9 of the cell lines used. In summary, integrated analysis of DNA methylation and gene expression between invasive and non-invasive melanoma cell lines has revealed a list of differentially methylated and differentially expressed genes that are potentially involved in the mechanisms associated with the invasive phenotype exhibited in melanoma cell lines.