Melanoma is the third cause of central nervous system (CNS) metastases and roughly 40–50% of advanced melanoma patients will develop CNS metastases. Importantly, the incidence of brain metastases may rise even further as systemic treatment of stage IV melanoma improves. In addition, CNS metastases are more frequent in BRAF-mutated melanoma. Finally, as responses in intracranial vs. extracranial sites may be heterogeneous, the efficacy of systemic therapy on brain metastases may be difficult to predict.1–4 Although the clinical survival outcomes of melanoma patients with brain metastases have been significantly improved due to major advances in systemic therapy, there still remain to be many challenges.