OBJECTIVES: To investigate the cost-effectiveness of Gefitinib relative to the other alternatives used for the first line treatment of EGFR mutation positive advanced lung cancer patients, including: gemcitabine/carboplatin, paclitaxel/carboplatin, vinolerbin/cisplatin, gemcitabine/cisplatin and pemetrexed/cisplatin, from a provider and payer perspective in Greece METHODS: A probabilistic Markov model was constructed with four health states: treatment response, stable disease, disease progression and death. Objective response rates, hazard ratios and utility decrements for Gefitinib relative to paclitaxel/carboplatin were obtained from a head-to-head trial (IPASS), while meta-analysis was used to estimate corresponding data for remaining comparators. Utilities were applied to estimate Quality Adjusted Life Years (QALYs). The databases of several hospitals were analyzed to estimate resource utilization. Unit prices were obtained from the most up to date official resources and reflect 2011. Outcomes were bootstrapped 5,000 times to deal with uncertainty and to construct uncertainty intervals (UI). A discounting rate of 3.5% was applied for all outcomes. RESULTS: Mean QALYs were: 1.10 (95%UI:0.89-1.28), 1.04 (95%UI:0.87-1.19), 0.95 (95%UI:0.80-1.05), 0.91 (95%UI:0.76-1.10), 0.90 (95%UI:0.77-1.00) and 0.87 (95%UI:0.73-0.99) for gefitinib, pemetrexed/cisplatin, gemcitabine/cisplatin, gemcitabine/carboplatin, paclitaxel/carboplatin and vinolerbin/cisplatin respectively. From a provider perspective, total treatment cost per patient was: €61,865 (95%UI:€52,848-€71,444), €72,817 (95%UI:€65,213-€80,014), €59,270 (95%UI:€52,830-€65,530), €60,842 (95%UI:€50,113-€71,343), €58,081 (95%UI:€53,237-€62,628) and €54,468 (95%UI:€46,874-€62,245), respectively. Hence, gefinitib dominates all other options apart from vinolerbin/cisplatin, which is the least costly option. The incremental cost per QALY gained  with gefitinib relative to vinolerbin/cisplatin, was limited to €9,662. Similar were the results from a payer perspective. The incremental cost per QALY gained in this case was €27,369. Probabilistic analysis indicated that at a 50,000 willingness to pay threshold gefitinib was cost-effective in 90% of cases in both perspectives of analysis. CONCLUSIONS: Gefitinib may represent a cost-effective choice, compared with alternative used in the first line treatment of mutation positive non-small cell lung cancer patients in Greece.