Brain metastases are common in stage IV malignant melanoma, carrying a prognosis traditionally regarded as severe, with a median survival of few months. Recently introduced systemic therapies as targeted therapy or immunotherapy have significantly improved the prognosis of metastatic melanoma. The optimal association of radiotherapy to such novel treatments has to be clarified. We report on a 43-year-old woman with 10 brain metastases. Three of them were treated with stereotactic radiosurgery (SRS) with complete response even of the untreated lesions. As the patient was BRAF-mutated, she was started on dabrafenib/trametinib. After 8 months she developed new brain metastases, which again responded to a new treatment with SRS. As after 7 months additional lesions appeared, she was treated with whole brain radiotherapy and was started on nivolumab. Twenty months after the first diagnosis of brain metastases the patient is fit without significant clinical and radiological signs of toxicity.