AbstractNext‐generation sequencing technologies are now common for whole‐genome, whole‐exome and whole‐transcriptome sequencing (RNA‐seq) of tumors to identify point mutations, structural or copy number alterations and changes in gene expression. A substantial number of studies have already been performed for melanoma. One study analysed eight melanoma cell lines with RNA‐Seq technology and identified 11 novel melanoma gene fusions. Whole‐exome sequencing of seven melanoma cell lines identified overlapping gain of function mutations in MAP2K1 (MEK1) and MAP2K2 (MEK2) genes. Integrative sequencing of cutaneous melanoma metastases using different sequencing platforms revealed a new somatic point mutation in HRAS and a structural rearrangement affecting CDKN2C (a CDK4 inhibitor). These latter sequencing‐based discoveries may be used to motivate the inclusion of the affected patients into clinical trials with specific signalling pathway inhibitors. Taken together, we are at the beginning of an era with new sequencing technologies providing a more comprehensive view of cancer mutational landscapes and hereby a better understanding of their pathogenesis. This will also open interesting perspectives for new treatment approaches and clinical trial designs.