Non-small-cell lung cancer (NSCLC) is the most common type of cancer representing 18.2% of all cancer deaths around the world and in Mexico the estimated mortality rate is 13.4 by 100,000 patients. OBJECTIVES: Evaluate gefitinib as first and second line treatment of locally advanced or metastatic NSCLC compared to available treatment alternatives in Mexico. METHODS: A two-way analysis was performed: (1) For the first-line treatment in patients with Epidermal Growth Factor Receptor Inhibition in Mutation-Positive Non–Small-Cell Lung Cancer (EGFR M+ NSCLC) a cost-minimization analysis was used comparing gefitinib versus erlotinib (Kim ST, 2012), also a Markov model was developed to perform a cost-effectiveness analysis evaluating gefitinib versus carboplatin+paclitaxel (Mok TS, 2009), with efficacy measure Progression-free survival (PFS); and (2) For patients in a second-line NSCLC treatment, regardless of EGFR mutation, a cost-minimization analysis was conducted comparing gefitinib versus docetaxel and pemetrexed (Hanna N, 2004) (Kim ES, 2008). The costs were obtained from institutional sources. An exchange rate of $13.12 MXN per USD was used. Sensitivity analyses were performed in order to test the robustness of the model. RESULTS: For first-line treatment, gefitinib was a cost-saving alternative respect to erlotinib, obtaining a cost differential of $9,710 USD in favor of gefitinib. To the same patients gefitinib compared to carboplatin plus paclitaxel generated an additional cost of $2,361 USD per patient, with additional PFS of 0.37 years and an ICER of $7,023. For second-line treatment gefitinib had a lower cost compared to pemetrexed and docetaxel, generating a saving per patient of $927 USD and $21,346 USD respectively. Robustness of results was confirmed by additional deterministic and probabilistic sensitivity analysis. CONCLUSIONS: The use of gefitinib for the treatment of locally advanced or metastatic NSCLC is a cost-saving alternative compared to erlotinib, pemetrexed and docetaxel, and also cost-effective compared to carboplatin plus paclitaxel.