Cutaneous melanoma, developed from cutaneous melanocytes, is an aggressive tumor - responsible for more than 80% of death from skin cancer - with an incidence that continuously increases all over the world. Vitiligo is an acquired skin depigmentation due the autoimmune destruction of melanocytes. This disease can be isolated, associated to other autoimmune disorders, or sometime associated to melanoma. Interestingly, development of vitiligo in melanoma patients is associated with a better overall survival. Melanoma is considered a very “immunogenic” tumor that can induce spontaneous anti-tumor responses. Even when these responses are detectable, they usually have a poor clinical impact, with no or very partial tumor regression. Many tumor escape mechanisms can explain this failure of the immune system to eradicate the tumor. Melanocyte-specific T cell responses, similar to those observed in melanoma patients, are detected in vitiligo patients. In this context these T cells do result in the destruction of melanocytes, and induce the autoimmune depigmentation of the skin. Studying why T cell with the same specificity are able to kill their target in one disease - vitiligo-, and inefficient in another – melanoma – is a way to optimize immunotherapy of melanoma.