OBJECTIVES: To describe treatment patterns by lines of systemic (drug) therapy in patients with metastatic melanoma in the United States. METHODS: Using a large US medical claims database, patients were identified between 2005 and 2010 using ≥2 melanoma diagnoses (ICD-9-CM: 172.xx, V10.82) and ≥2 diagnoses for metastasis (ICD-9-CM: 197.xx, 198.xx). Patients were followed from the metastatic diagnosis date to death, disenrollment, or end of study period (6/30/2010), whichever occurred first. Lines of systemic therapy were identified based on the temporal order, gaps, and changes in the drug regimens. Systemic therapies and the duration of therapy in each line were examined. RESULTS: A total of 2546 patients with metastatic melanoma were included and 985 (38.7%) received systemic therapy. As the first documented therapy after diagnosis, 82.4% of patients received mono-therapy (38.5% temozolomide, 14.3% interleukin-2, 11.4% interferon alfa-2b, 8.2% dacarbazine, 2.9% paclitaxel, 2.5% GM-CSF) and 9.4% received carboplatin plus paclitaxel. Mean duration of mono-therapy was 60 days, ranging from 32 days on interleukin-2 to 124 days on GM-CSF. Of 287 patients (29.1% of previously treated) received subsequent therapy, 68.0% received mono-therapy (26.8% temozolomide, 11.9% interleukin-2, 10.5% dacarbazine, 8.4% paclitaxel, 3.1% interferon alfa-2b, 1.7% GM-CSF), 16.7% carboplatin plus paclitaxel, and 7.3% dacarbazine-containing therapies. Mean duration of mono-therapy was 67 days, ranging from 30 days on interleukin-2 to 238 days on GM-CSF. Among 71 patients who further received additional therapy, mono-therapy was still the dominant regimen (63.4%) with 21.1% temozolomide, 18.3% paclitaxel, 8.5% interleukin-2, 5.6% dacarbazine, 4.2% GM-CSF, and 1.4% interferon alfa-2b. Carboplatin plus paclitaxel was given to 19.7% of patients. Mean duration of mono-therapy was 63 days, ranging from 7 days on interferon alfa-2b to 90 days on temozolomide. CONCLUSIONS: The majority of patients with advanced melanoma didn’t receive systemic therapy as captured in the claims database; among those who received systemic therapy, mono-therapy was most common.