Leptomeningeal disease (LMD) from melanoma is rapidly fatal with median overall survival between 6.9 weeks and 3.5 months. It is not known whether immune checkpoint inhibitors have a role in treating LMD. We report a 33-year-old male patient who developed LMD from a BRAF V600E-mutated melanoma brain metastasis, despite prior treatment with surgical resection, radiotherapy and dabrafenib/trametinib. He underwent whole brain radiotherapy with stereotactic radiotherapy to the lumbosacral spine, and was started on nivolumab, which led to prolonged remission lasting 2 years and 3 months, before disease progression and death. This is the first case report to highlight a potential long-term efficacy of radiotherapy and anti-PD-1 immunotherapy, in treating LMD from metastatic melanoma that is resistant to targeted therapy.