Primary melanomas evolve from melanocytes or from precursor lesions through two stages: the radial and vertical growth phases. The radial growth phase may be in situ or microinvasive, but is a non-tumorigenic neoplastic process, while the vertical growth phase is tumorigenic. The prognosis in radial growth phase is excellent irrespective of thickness or other variables. Curable radial growth phase melanomas can be recognized by surveillance of patients identified by screening for risk markers which include dysplastic nevi, common nevi, freckles, and other indicators of chronic or acute sun exposure or sun sensitivity. The prognosis in vertical growth phase depends on attributes of the tumor and of the host. The tumor mitotic rate, the presence of host tumor-infiltrating lymphocytes (TIL) within the vertical growth phase, and tumor thickness are the most powerful predictors of survival. New prognostic attributes are needed not only to provide for more accurate prognosis and diagnosis, but also to test the relevance of in vitro or animal studies in a human neoplastic system. Such attributes will be developed in the future based on markers that are associated with tumor progression. Candidate markers include growth factors and cytokines and their receptors, adhesion molecules and their ligands, chemotactic and motility factors, immune response-related molecules, and tumor-associated proteases. Some of these markers that are represented in the transition from radial to vertical growth phase will be reviewed. The tumor progression model presented here has been of value in the development of more accurate prognostic models, and in the elucidation of mechanisms of the malignant phenotype in melanoma.