MeLiM is a pigmented minipig breed that spontaneously develops cutaneous melanomas. These melanomas appear during the first months of life and may ulcerate and produce metastasis to other organs. Following an exponential growth during the first weeks, nearly all lesions spontaneously regress: they dry, progressively whiten and completely disappear. This process is often accompanied by a depigmentation of the coat, hair and eyes of the animal. A total remission occurs. We aim at studying the immune response during melanoma progression till first signs of regression. We phenotyped 74 lesions sampled from 3 to 49 days-old piglets. Three groups of 20-32 lesions were established according to age and signs of histological regression: group I, 3-12 days of age and no signs of regression; group II, 13-42 days of age, no signs of regression and group III, 19-49 days of age, with histological signs of regression. Lesions size increased from group I to III. Group I comprised lesions with higher ulceration rate while group III lesions had stopped enlarging in size and displayed a lymphocytic infiltration. Flow cytometry analyses of dissociated tumours showed a circa 6-fold increase in CD45+ cells detected in MeLiM growing tumours (group I compared to groups II and III). Most abundant cell types were myeloid cells, more particularly macrophages and neutrophils. Most variable cells during progression were macrophages with different phenotypes (MHCII, CD14, CD163) showing different dynamics. During first regression stage, macrophages subtypes continued to evolve and a further increase of T cells as well as DC subpopulations was detected. The study of the MeLiM model can unveil successful immunological melanoma regression mechanisms without adverse secondary effects other than depigmentation.