The brain is one of the most frequent locations of metastasis in malignant melanoma. We aimed to identify prognostic factors for overall survival (OS) and local tumor control (LC) in patients with malignant melanoma metastasized to the brain treated by multimodal therapy. All patients diagnosed with malignant melanoma brain metastases between 1992 and 2011 at a single center were registered (n=100, 65% male, 35% female). OS and LC of individual brain metastases were retrospectively analyzed. Subgroup analyses was performed in patients with multiple brain metastasis (n=35) and LC per lesion (n=72) was evaluated in 37 patients. Median age was 57 (27-81) years. Fifty-three percent of patients had 1-2 brain metastases, 47% had >2 and 71% presented with additional extracranial metastases. Primary treatment included systemic therapy alone (temozolomide/fotemustine, 14%), local therapy (surgery and/or stereotactic radiotherapy, 25%), whole-brain radiotherapy (WBRT, 10%), combined WBRT and systemic therapy (18%), local therapy plus WBRT (5%) and combination of local and systemic therapy (8%). Three percent received a tri-modal therapy (WBRT, local and systemic therapy) and 17% refused treatment. Median follow-up in surviving patients was 32 (4-222) months, median OS in all patients 3.9 months (1-year survival 21.4%). Local therapy (p<0.001), systemic therapy (p=0.002), number of brain metastases and primary therapy including a local therapy (p<0.001) were significantly associated with OS. In the subgroup with multiple brain metastases (n=35), a trend (p=0.058) for improved OS after initial treatment with WBRT plus systemic therapy was noted (median OS 3.8 months) and use of these two modalities over the course of the disease was significantly associated with OS (p=0.007). The best LC per single lesion (n=37) could be achieved by combination of local with systemic therapy (p=0.011). Number of brain metastases, extracranial metastases and use of local therapy are independent prognostic factors in melanoma metastatic to the brain. LC and OS can be improved by combining local with systemic treatment. In patients with multiple brain metastases, WBRT plus systemic therapy provides superior OS.