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Melanoma is the most aggressive skin tumour and the§number of cases and deaths has increased faster than§many other cancers. Activating mutations in the B-RAF§and N-RAS proto-oncogenes and deletion of the tumour§suppressor gene CDKN2A occur at high §frequencies in melanomas. This study characterises§the widely unknown consequences of the most prominent§somatic alterations in the B-RAF, N-RAS, and CDKN2A§genes on gene expression in melanoma. Additionally,§the effect of the V600E B-RAF mutation on gene§expression in benign melanocytic nevi, known§precursors of melanoma, was examined. In summary, the§studied alterations significantly influence§expression of various genes in the RAS-RAF-MEK-ERK,§Rb, and PI3K/AKT pathways. MAPK pathway activation§occurs in the early stages of melanocyte§transformation, antagonised by several tumour§suppressing mechanisms. Among others, CDKN1C was§identified as novel gene, whose loss most likely§constitutes a second genetic hit required for§melanoma progression. Besides new therapeutic targets§to treat melanoma patients, the data may encode new§markers for early recognition of§individuals with increased risk for development of§malignant melanoma.