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The relationship between melanocyte stem cells (MCSCs) and melanoma has been unclear. We recently demonstrated that melanoma-prone MCSCs are able to initiate cutaneous melanoma following stem cell activation through ultraviolet-B (UVB) exposure or natural stem cell cycling. Conversely, MCSC quiescence is sufficient to suppress tumorigenesis. This provides new insight into the role of environmental factors in tumor initiation from adult stem cells.