Approximately one third of patients with cutaneous melanoma later develop a metastatic disease, having then an extremely poor rate of survival. Because of the highly unpredictable nature of melanomas, finding those patients who are likely to develop a metastatic disease and those patients who probably will survive is an ongoing challenge. The current "conventional" prognosticators, such as Breslow thickness, Clark level of invasion, and ulceration, cannot perfectly predict the clinical course of this disease at an individual level. Although the sentinel lymph node biopsy procedure and reverse transcription polymerase chain reaction techniques have significantly improved the staging of patients with melanoma, new molecular prognostic markers may help in selection of appropriate patients for strenuous adjuvant therapies and for randomized clinical trials. Furthermore, these markers also improve our basic understanding of the biology of cutaneous melanoma, potentially offering new targets for novel treatment strategies. This paper reviews the current literature on transcription factors and other dysregulated proteins involved in melanoma prognosis.