Background Morphologic and histopathologic markers have been the backbone for the classification and prognostic assessment of melanoma. Availability of an increasing number of molecular markers, however, provides the potential for refining diagnostic and prognostic categories in this disease. Methods We reviewed the recent data that are accumulating concerning gene expression and genetic profiling and related these to clinical aspects of the disease. Results Multiple biomarkers have now been described, and their biologic significance is being established. In addition, several candidate molecules involved in mela-noma pathogenesis have been identified. Conclusions The process of biomarker identification and validation is providing a rapidly changing molecular view of melanoma, a strategy that is necessary for developing truly stratified or even personalized prevention or management.