OBJECTIVES: This study estimates the impact of Non-Small Cell Lung Cancer (NSCLC) on population health levels and its economic impact in Portugal in 2012.   METHODS: Data from a cohort of 581 patients with NSCLC completed with an expert panel was used to develop a model of cumulated prevalence with a 6 months cycle period and a time horizon of 5 years. The impact on health status was measured using the Disability Adjusted Life Years (DALYs). The economic impact analysis includes two components. The first estimates the direct costs generated by NSCLC including consumption of inpatient care and outpatient care (consultations, medication, diagnostic exams, transportation, etc). The second estimates indirect costs related to loss of productivity due to NSCLC. RESULTS: A total of 3,180 deaths in Portugal in 2012 were caused by NSCLC, which corresponds to 2.0% of the total deaths in Portugal. The DALYs resulting from premature deaths caused by NSCLC in 2012 totaled 25,071 representing 4.5% of years lost generated by all deaths in the country. For 2012 it is estimated that 3,236 life years were lost due to disability. The total disease burden attributable to NSCLC is thus estimated at 28,307 DALY. The estimated direct cost generated by NSCLC was € 89 million and that total can be broken down into € 32 million for inpatient care and € 57 million for outpatient care. The indirect costs must also be taken into account and they added up to € 54 million. The economic burden of NSCLC is substantial, totaling € 143 million, about 0.09% of Portuguese GDP and 0.92% of all Portuguese health spending in 2012. CONCLUSIONS: NSCLC is an important cause of disease burden and costs in Portugal and should receive adequate attention from policy makers.