Currently, the treatment of malignant melanoma offers the longest and the most studied experience of innovative treatments in malignant pathology. The algorithm of the therapeutic decision in advanced or metastatic melanoma must comprise: the timing of the therapeutic initiation, the sequencing of the specific oncological treatment (radiotherapy and chemotherapy still being therapeutic alternatives in selected cases), the diagnosis and the management of adverse reactions. We present the case of a patient diagnosed with metastatic malignant melanoma in November 2019, who progressed successively under new systemic treatment throughout the 3 years of treatment and experienced skin reactions of various degrees of severity. The comprehensive response to secondary hilar pulmonary lymphatic determinations under subsequent chemotherapy was specific to the presented case. The occurrence of vitiligo secondary to immunotherapy is a favorable prognostic factor, but the occurrence of secondary cerebral determinations is an extremely severe prognostic factor in malignant melanoma and a challenge in making the therapeutic decision. Previous treatment with immune checkpoint inhibitors may trigger a favorable response to systemic chemotherapy. The early and accurate diagnosis of the adverse events of the new therapies requires a multidisciplinary approach, because it can radically change the therapeutic decision.