OBJECTIVES: In the context of a payment mechanism construction for submitting a proposal to the Chilean National Health Fund and on the basis that current payment mechanisms do not consider accurate reviews on the actual costs of diseases, it was necessary to develop an efficient and realistic strategy for costs estimation. The aim of this work was to estimate direct costs associated to NSCLC by using an efficient and appealing methodology for the public insurance. METHODS: A cost study based on a hybrid and novel methodology was conducted. An specialty facility and physicians familiar with the disease were identified. Clinical pathways were developed according to real clinical care and supplies consumed (variable: quantity). These results were matched with statistic data provided by local information system and complemented with national-official price lists (variable: price). RESULTS:  Comprehensive clinical pathways reflecting clinical behaviour were developed (payment base), allowing micro-costing. Patients routes were also identified (frequencies). Afterwards, costs per disease-stage were obtained at patient level and population level (Total Cost for all stages and full treatments coverage: USD 4.077.000 (n=350 cases); Most expensive stages -IIIB and IV stage- UDS 2.141.762 (n=25 cases), which represents the 52% of expenditure. Equity costs were defined as barriers preventing patients from a specialized treatment, these were also calculated: USD 302.000 (n=25 cases). Tyrosine Inhibitors (2^nd line high-cost treatment) represent the 28,05% of expenditure. By including novel strategies for funding, inmunotherapy represents only a 3,81% of the High-Cost Fund, making feasible including these drugs at the current expenditure level. CONCLUSIONS: A cost study of high internal validity was achieved. The role of specialty facilities and medical teams it is crucial towards a more efficient and clinically validated costs studies, based on clinical pathways reflecting the accurate consumption and evidence-based medical behaviour. Based on these data, a proposal was submitted for promoting immunotherapy coverage.