The central nervous system (CNS) is a favourite site of metastasis in advanced melanoma and, despite the improvement obtained in the control of brain metastasis, most patients die as a result of extracranial progression of the disease. CNS primary malignant melanoma is a rare entity and the diagnosis is generally made after the exclusion of a primary cutaneous or mucosal/retinal malignant melanoma, as differential histological diagnosis between primary and metastatic origins is often difficult. From a review of the literature, patients with primary brain melanoma or exclusive (and limited) brain metastasis in the absence of extracranial melanoma present a relatively good prognosis if adequately treated with aggressive locoregional treatments (neurosurgery and/or radiotherapy) and, later, with drugs able to cross the blood-brain barrier (i.e. fotemustine). In this letter, we describe the history, treatment and favourable clinical outcome of two patients with melanoma and CNS as the exclusive site of disease.