A 49-year-old patient with metastatic melanoma was treated with nivolumab (Opdivo). An early F-FDG PET/CT after 2 cycles showed a progressive metabolic disease. A 4-month optimal follow-up F-FDG PET/CT showed a complete metabolic response. The treatment was stopped after 22 cycles because of immunotherapy-related pneumonitis. After discontinuation of treatment, PET/CT examinations demonstrated a metabolic complete remission during 2 years. The metabolic pattern on early PET was suggestive of pseudoprogression, which is a rare phenomenon reflecting an activation of inflammatory cells within the tumor microenvironment causing lesions to increase in size and to accumulate FDG until a sufficient immune response is developed.