Although good prognostic markers are already available for patients with cutaneous melanoma, there still is a need for additional markers that are helpful to assess prognosis in individual patients. These so-called progression markers are likely to be found in molecules that play a role in the process of metastasis. Here, emphasis is put on the potential clinical implications of studies on the adhesion molecules from the integrin and CD44 families, proteases of the plasminogen activation system, and components involved in angiogenesis. Based on their differential expression in melanocytic tumor progression, several molecules of these categories appear promising for prognostic and diagnostic purposes. In this respect, the parallelism between key processes in the pathogenesis of metastasis and of angiogenesis is noteworthy. As technical developments in molecular pathology are relevant for diagnostic and prognostic purposes, some recent applications are discussed. An integrated molecular approach in a proper clinicopathologic context is advocated, including proper quality control measures.