Recently, several important findings on melanoma development and progression have accelerated progress towards a molecular understanding of melanoma biology. Furthermore, the development of experimental tools, such as a wide range of cell lines and animal models of metastasis, has turned melanoma into a model for general tumour research. However, it has also become evident that melanoma is distinct from other tumours with regard to its cellular origin and pathophysiological mechanisms. This review focuses on important new findings that have contributed to a greater understanding of the molecular processes leading to melanoma. Translating these innovative new results into potent therapeutic approaches will require even more effort. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.