Cutaneous melanoma (CM) is the most lethal skin malignancy, with a constant increase in incidence. These tumors show a biological behavior unpredictable by the classical parameters Moreover, conventional therapies are ineffective to treat advanced stage case. Therefore, the identification of molecular alterations involved in their biological aggressiveness represents a major challenge for researchers. Accumulating evidence supports the involvement of cancer stem cells (CSC) in initiation, progression, chemoresistance and therapeutic failure of malignant melanoma, and the aggressive subsets of melanoma cells have been frequently associated with molecular markers shared by stem cells.