INTRODUCTION: Primary melanocytic tumours of the leptomeninges are rare diseases. The WHO classification of 2007 described four entities: diffuse melanocytosis, melanocytoma, malignant melanoma and meningeal melanomatosis. Meningeal melanocytosis is a benign proliferation of melanocytes with a risk of malignant transformation and is often associated with neurocutaneos melanosis. CASE REPORT: A 65-year-old male patient presented with low back pain and disturbed micturition. Neurological examination revealed left sided S1- sensory radiculopathy. His medical history was unremarkable. MRI of the lumbar spine showed a contrast-enhancing intrathecal tumour of the conus medullaris and MRI of the brain was suspicious of neoplastic meningitis. Spinal surgery exhibited a brown tumour mass with diffuse spreading of pigmented lesions along the arachnoidea. Histological, immunohistochemical, and molecular analyses showed an intrathecal melanoma with a wild-type BRAF genotype. Dermatological examination was unremarkable. Lumbar stereotactic radiotherapy was applied. Subsequently, 3 cycles of temozolomide (150mg/m2 on 5 days out of 28) and bi-weekly intrathecal liposomal cytarabine were administered. Despite the poor prognosis of neoplastic meningitis in melanoma, the patient survived without clinical for more than one year. 15 months after the initial diagnosis spinal MRI showed a local relapse and a second surgery was performed. This time molecular analysis of the tumor revealed the presence of the BRAF V600E mutation. Due to the initially slow tumor progression treatment with B-Raf inhibitors was withheld and immunotherapy with the anti-CTLA-4 antibody ipilimumab was initiated together with stereotactic radiotherapy of the conus medullaris. Three months later, the patient complained about diplopia and dizziness. Neurological examination revealed oculomotor nerve palsy. MRI of the brain showed a meningeal contrast-enhancement in the brainstem area. The B-Raf inhibitor vemurafenib was initiated in combination with intrathecally administered liposomal cytarabine and whole brain radiotherapy. Despite this the patient's condition deteriorated and he died two weeks later. Considering the long progression-free interval and the diffuse intrathecal melanocytic spread, the initial diagnosis of neoplastic meningitis was re-evaluated. Differential diagnoses include neoplastic meningitis from an unknown primary melanoma and malignant transformation of leptomeningeal melanocytosis. Retrospectively, we speculate that the patient had a leptomeningeal melanocytosis and consecutive malignant transformation. Treatment options are palliative and include intrathecal and systemic chemotherapy, radiotherapy, immunotherapy, as well as kinase inhibitors. Since evidence based guidelines are lacking therapy has to be selected on an individual basis.