Several intracellular sources of ROS have been proposed in melanoma cells [37–39], such as the mitochondrial electron transport chain [40], considered the major source in metabolically very active tumor cells, NADPH oxidases (mainly Nox4) [41,42] and, as unique feature of these melanocytes-derived tumor cells, the aberrant melanin biosynthesis and oxidation [43]. Here, NOX4 is linked to neoplasm.