Immune reactions against cutaneous melanocytes are valuable models for understanding melanoma pathophysiology and for development of effective targeted cancer treatments. In this chapter, we aim to review the immune mechanisms involved in destruction of melanocytes which have been described in melanoma patients, as well as to discuss the significance of clinical expression of these resulted depigmentations: melanoma regression, vitiliginous depigmentation related to melanoma, and halo (Sutton) nevi related to melanoma. We discuss in this chapter the immunological background of anti-melanocyte reactions described in melanoma and we present the morphological consequences of these destructive phenomena, from microscopically, dermatoscopically, and clinical points of view. A comprehensive discussion regarding vulgar vitiligo or Sutton nevi in general population is beyond our scope, as this chapter is focused on melanoma’s associations.