OBJECTIVES: Economic evaluation is increasingly important in appraisal of innovations in oncology, requiring accurate costing estimations. The MELISSA study aimed at assessing hospitalization costs of metastatic melanoma in France. METHODS: A retrospective cohort analysis from French Medical Information System Program (PMSI, “Programme de Médicalisation des Systèmes d’Information”) for years 2011-2013 was conducted. The study population consisted of all treatment naïve, incident adult patients hospitalized with metastatic melanoma diagnosed from 1 Jan 2011 with follow-up until 31 Dec 2013 or death, whichever occurred first. Melanoma diagnosis and metastatic status was obtained using ICD-10 classification (melanoma: C43, metastatic status: C77, C78, C79). Patients were allocated to pre-progression  and post-progression health states of the disease using progression markers, defined with clinical experts as the occurrence of either new or brain metastases, palliative care, or occurrence of both palliative care and brain metastasis or treatment switch,  identified by specific ICD-10 code. Mean annual and monthly hospitalization costs (primary objective) per patient were estimated using French tariffs and production costs, adjusting for annual deaths in both inpatient and outpatient settings. Secondary objectives consisted of mean annual/monthly costs of chemotherapies/immunotherapies, treatments-associated clinical events, palliative care and transportation. RESULTS: The cohort enrolled 8,862 patients. There were 7,332 patients (53% male) in pre-progression (26,843 hospital stays), 5,062 patients (56% male) in post-progression (36,425 hospital stays), and 3,479 hospital deaths. Costs expressed as mean annual production costs/patient-year were in pre-progression: 4,973€ for hospitalization, 23,047€ for chemotherapies/immunotherapies, 4,177€ for clinical events and 619€ for transportation. In post-progression: 32,320€ for hospitalization, 17,884€ for chemotherapies/immunotherapies, 8,827€ for clinical events, 19,894€ for palliative care and 2,536€ for transportation. CONCLUSIONS: In metastatic melanoma in France, treatment costs accounted for the highest share. Except treatments, disease progression was associated with a tangible increase of hospitalization and other costs. These estimated hospital costs will be useful to populate cost-effectiveness models.