OBJECTIVES: EGFR testing and first line tyrosine kinase inhibitor (TKI) for patients with activating mutations is an option for the treatment of advanced non-small cell lung cancer (NSCLC). There is few data’s on the cost-effectiveness of this strategy. The objective of this study was to determine the incremental cost-effectiveness ratio of first-line treatment with TKI compared to recommended chemotherapy (cisplatin pemetrexed doublet) in patients with EGFR mutation. METHODS: A Markov model was developed. Clinical outcomes were derived from the EURTAC phase III trial comparing TKI to chemotherapy in first-line of NSCLC. Cost data were estimated using individual data from French randomized clinical trial or prospective cohort, whereas utility scores derived from published data’s. Costs were limited to direct costs for medications, physician visits, hospitalizations and treatment of adverse events. Analysis was limited to the period between treatment initiation of until first progression.  All costs were expressed in 2010 Euro. Sensitivity analyses were performed. RESULTS: First line treatment with TKI was more effective than recommended chemotherapy (respectively 0.730 and 0.437 QALY), but also more expensive (respectively 29 702 € and 18 796 € per patient). The incremental cost-effectiveness ratio was then estimated at 37 221 €/QALY. Sensitivity analyses showed the robustness of the results. CONCLUSIONS: Based on these data, first line treatment based on TKI appeared as cost effective in EFGR mutated advanced NSCLC patients.