OBJECTIVES:  To evaluate the direct medical costs (DMC) in patients with lung cancer treated with gefitinib or erlotinib in first line and subsequent therapies. METHODS:  The Orizon is an administrative database containing over 18 million lives of the Brazilian Private System. Eligibility criteria were patients treated in first line with any TKI with ICD-10 code C34 from 2013 to 2015. Monthly DMC were calculated as the sum of medical claims for each patient during treatment and all results were represented by the mean values with an exchange rate of 1 USD = 3.23 BRL. RESULTS:  A total of 55 patients were treated with any TKI in first line. Results of DMC in gefitinib group was USD 1,463.32 (BRL 4,726.54) per month, while the erlotinib group was USD 4,369.77 (R$ 14.114,37), resulting in an average cost increase of 2.9 times, mainly due to the higher erlotinib cost and hospitalizations. In terms of length of treatment (LOT) results were similar between both medicines, patients were on gefitinib therapy for 7.6 months and erlotinib for 7.9 months. We also evaluated 26 patients in second line, after TKI therapy, where the most common were pemetrexed monotherapy or in combination with other drugs resulting in a monthly DMC of USD 5,492.50 (R$ 17,740.78) with a LOT of 5.0 months and bevacizumab plus chemotherapy with a monthly DMC of USD 11,134.98 (R$ 35,966.01) and a LOT of 4.8 months. CONCLUSIONS: Monthly costs with patients treated in first line with gefitinib were lower than erlotinib and presented a similar mean length of treatment duration. It was noteworthy that monthly costs of precision medicine therapies were much lower than chemotherapy schemes in the Brazilian private setting.