The intracerebral response rate (RR) to vemurafenib in patients with B-RAF mutated melanoma brain metastasis was assessed. Patients with B-RAF-positive metastatic melanoma and asymptomatic brain metastases at initiation of vemurafenib were eligible. Records were analysed retrospectively to calculate the RR, duration of responses, time to central nervous system (CNS) progression and overall survival. Twenty-two patients with CNS metastasis received vemurafenib (male : female=13 : 9; median age 49); 12 had received no previous local therapy to the brain (group A), six had undergone previous surgery and/or radiotherapy with residual disease (group B; n=6) and four patients had received previous local therapy to the brain but with evidence of progression in the CNS before the start of vemurafenib and were included in group A (n=12+4=16). A 50% RR was observed in group A. Duration of responses was between 8 and 32 weeks. Similarly, a 50% RR was observed in group B; however, the contribution of vemurafenib to CNS control in this group was more difficult to assess. The duration of responses in group B was 4–33 weeks. All except two patients progressed in CNS before, or at the time of, systemic progression. The median time to CNS progression for the entire cohort was 23 weeks (range 12–60) in responding patients and 14 weeks (3–22) in those without a response. The median overall survival was 46 weeks for the patients with an objective response and 21 weeks among the nonresponding patients. Vemurafenib resulted in a 50% CNS RR. A prospective assessment of the medication in patients with B-RAF mutated melanoma cerebral metastases is warranted.