Malignant melanoma patients frequently relapse with metastases in the brain, making it the third most common cancer-causing brain metastases in the USA. Management of brain metastases remains challenging because of the rapid progression of disease and ineffectiveness of conventional therapies. This retrospective study, with a ‘pre/post’ design, quantifies the economic burden of brain metastases among melanoma patients in the USA. A large managed-care insurance claims database (2000 Q1–2011 Q3) was used to identify patients with melanoma and brain metastases. The preperiod was defined as the 6 months before the index date (diagnosis of first observed brain metastases) and postperiod as the period following the index date up to 12 months. All-cause and brain metastasis-related healthcare resource utilization and healthcare costs were compared on a per-patient-per-month (PPPM) basis between preperiods and postperiods. The study included 6076 patients (mean age 63.4 years); 57.6% were men. Significant differences (P<0.0001) were observed between the postperiods and preperiods in the mean all-cause and brain metastasis-related PPPM hospitalizations and emergency department and outpatient visits. Significant postperiod versus preperiod differences were also observed in the PPPM mean (standard error) all-cause healthcare costs [total: $14 489 ($231) vs. $7277 ($116); inpatient: $6330 ($195) vs. $1900 ($69); outpatient: $6609 ($102) vs. $4449 ($79); P<0.0001 for all] and brain metastasis-related costs [total: $6542 ($145) vs. $1933 ($62); inpatient: $2976 ($118) vs. $472 ($39); outpatient: $3451 ($76) vs. $1413 ($47); P<0.0001 for all]. Radiotherapy was the most common treatment. The economic burden associated with brain metastases in melanoma is significant and underscores the need for newer therapies to improve outcomes in these patients.