7577 Background: Driver mutations occur in genes that encode signalling proteins critical for cellular proliferation and survival. In lung cancer, these mutations include EGFR, KRAS, BRAF and EML4/ALK. Methods: We evaluated the feasibility of screening 228 NSCLC patients in Colombia by analyzing tumor tissue by DNA sequencing. Results: The study included 152 females (67%) and 76 males (33%) with a mean age of 59 (SD ± 13); 63% of the patients had adenocarcinoma, 6% presented non-specific tumors, 1.8% had large cell carcinomas, 2.6% had squamous cell carcinomas. Histological subtype was non-specific in 12.3%. According to tobacco consumption (n=173), 60%, 20% and 3% were non-smokers, ex-smokers or active smokers respectively. 57 patients had activating mutations (25%) in the EGFR, 40 with E19 deletion (70% of mutated subjects) and 17 with the in-frame L858R mutation (30%). Almost all with the E19 deletion were non-smokers (86%), as well as those affected by the E21 mutation (75%). 11% of tumors were positive for K-ras mutations (n=114), one patient (3.8%) was positive for the ALK/ELM4 fusion gene (n=26). BRAF (V600E) mutations were not detected (n=60). Conclusions: The frequency of mutations in EGFR in NSCLC patients from Colombia was greater than that reported in other western countries; the distribution favoured the presence of the E19 deletion and the proportion of ALK/ELM4 is in agreement with previous data. To our knowledge, this study represents the first comprehensive analysis of major oncogenic mutations found in a large cohort of lung cancers from Latin America.