OBJECTIVES:  To describe treatment patterns, direct costs and comorbidities in a population of patients with melanoma. METHODS:   Starting from ARNO Observatory, an Italian population-based patient-centric system through record linkage of 11 million inhabitants, we identified a cohort of patients with melanoma (ICD-9 code: 172 and/or V10.82) during 2009.  Discharge records, reimbursed prescription patterns, lab tests and diagnostic examinations were analyzed for 365 days after and before the accrual period. RESULTS: On a total of 2,962,498 subjects observed, 594 patients were hospitalized for melanoma (53.4% males) during 2009 (prevalence rate: 20.0 per 100,000).  Among them, 43% had at least one chronic comorbidity, hypertension is the most common (14.6%) followed by combination of dyslipidemia and hypertension (3.0%).  Therapy for melanoma is made both in and outside the hospital. Interferon alfa-2b was the most prescribed treatment outside the hospital with an average cost of €110, followed by Temozolomide (€40.7) and Erythropoietin (€39.6).  During one-year of follow-up, 13% of patients was hospitalized for chemotherapy with an average cost of €7398. This amount covers also drug treatment cost during hospitalization.  The average yearly cost/patient for population with melanoma was €4777 (hospitalizations: 70.8%, drugs: 14.4%, diagnostic examinations: 14.8%), with an higher cost for the subgroup of patient already in treatment the previous year before the accrual period (€6156 vs €4361). If we consider the subgroup of patient with metastatic melanoma (N=176), the overall cost rises at €15,984, most of it (60%) due to drug costs for specific therapy of melanoma and chemotherapy. Surprisingly methotrexate and cyclophosphamide appear in the top five list of prescribed drugs. CONCLUSIONS: This study shows high cost of patients with melanoma and how real world practice therapy, especially for metastatic melanoma, seems to be far from the guidelines recommendation. This suggests to create a regional network to correctly redirect therapeutic choices.