OBJECTIVES: Metastatic Melanoma (MM) is associated with serious clinical and humanistic burden. This study calculated the cost and medical resource utilization attributable to MM in a large geographically diverse commercially insured US population. METHODS: The MEDSTAT MarketScan® database (1/1/2000–12/31/2008) identified patients aged ≥18 years with ≥2 melanoma claims (ICD-9-CM 172.xx, V10.82), or ≥1 melanoma claim and ≥1 chemotherapies. After excluding patients with other malignant tumors and those with <1 month post-index or <6 months of pre-index, 2 mutually exclusive cohorts were formed. Patients with diagnosis of metastasis or related chemotherapies were categorized as MM, and the remaining as non-MM. Index-date was the first date of diagnosis of melanoma or MM respectively. Mean estimates of per-patient-per-month (PPPM) resource utilization and cost (in 2008 dollars) within each group (pre vs. post) were statistically compared. Attributed cost of metastasis was the difference in mean differences (post - pre) between the groups. RESULTS: The study identified 407 MM and 13,796 non-MM patients (mean age 48.8 and 47.8 years, respectively). For the MM patients, PPPM utilization increased 3 to 12 times from the pre-metastatic period (inpatient: 0.007 to 0.090, emergency room: 0.010 to 0.044, office: 0.724 to 2.592, all with p<0.0001, and hospital outpatient: 0.226 to 1.029, p=0.0442), while the PPPM total cost increased 7 times ($803.2 to $5,439.9, p<0.0001). For the non-MM patients, utilization increased marginally following melanoma diagnosis (inpatient: 0.005 to 0.008, emergency room: 0.012 to 0.016, office: 0.696 to 1.214, and hospital outpatient: 0.136 to 0.291, all p<0.0001). The total cost for non-MM patients doubled following diagnosis of melanoma ($432.3 to $955.2, p<0.0001). Upon metastasis, the disease attributed cost increased 9 times ($523 to $4638). CONCLUSIONS: The cost burden from resource utilization increases substantially with metastasis of melanoma.  Treatments that significantly delay disease progression in these patients will reduce this burden.