OBJECTIVES: To estimate health care resource use (HCRU) associated with the advanced melanoma management in Portugal and to calculate the resulting direct medical and non-medical costs. METHODS: An expert panel with 6 clinicians from the main Portuguese centers treating patients with advanced melanoma was created and assessed to estimate HCRU associated with the disease management. A two-stage modified Delphi technique was adopted. During the 1^st round experts answered to a questionnaire concerning resource consumption associated with different phases of disease management. At the 2^nd round experts discussed and validated the mean results obtained from the questionnaires, during a consensus meeting. Phases of disease considered were: treatment initiation, progression free, post-progression and terminal care. HCRU during progression free phase was estimated for two different subsets of patients, according to their previous treatment experience: ipilimumab-naïve patients and ipilimumab previously treated patients. Medical appointments, laboratory tests, imaging examinations, hospitalizations, radiotherapy/radiosurgery and concomitant medications were the resources considered. HCRU resulting from adverse events management was not included. Costs for each phase were obtained by multiplying mean estimates of HCRU by unit costs according to official sources. Oncology drugs costs were not included during the treatment phase. RESULTS: Elicited costs per disease management phase were the following: 893.4 € for treatment initiation, 1280.4€/3 weeks and 1487.5€/3 weeks for treatment phase, respectively for ipilimumab-naïve and ipilimumab previously treated patients. For the BSC phase the cost estimated was 1668.7 €/month and the total terminal care cost was 5920.8€. CONCLUSIONS: Inpatient costs assumed major role during all phases (except treatment initiation). Patient monitoring through medical appointments, laboratory tests and imaging examinations had a higher share of resource consumption during treatment phase than for patients on BSC. The results from our research are of utmost importance to support the cost-effectiveness evaluation of new advanced melanoma treatment strategies.