Melanoma is an ‘immunogenic tumor’, often highly infiltrated with lymphocytes, which are capable of inducing regression of the primary tumor. The commonly observed phenomenon of regression suggests substantial cross-talk between immune cells and transformed melanocytes. An immune response to melanocyte differentiation antigens common to transformed and normal melanocytes manifests clinically at distant sites as melanoma-associated vitiligo or halo nevi. Despite similar antigenic targets, the pathogenesis and prognosis differ between the different melanoma-associated leukodermas. Understanding immunologic cross-talk between melanocytes and the immune system will aid the development of approaches to combat melanoma.