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Background: In recent years, the discovery of predictive biomarkers has enabled the development of targeted therapies that have improved the prognosis of patients with non-small cell lung cancer (NSCLC). No data are available at present on the molecular profile of NSCLC in Reunion Island, a French overseas department located in the Indian Ocean and characterized by an ethnically-mixed population., Method: This observational, retrospective, and multicenter study included all patients who were diagnosed with NSCLC in Reunion Island during 2 years and whose tumor specimens were sent for molecular analysis at Bordeaux University Hospital. The aim of the study was to determine the molecular profile of NSCLC in the Reunionese population, including the frequency of epidermal growth factor receptor (EGFR) mutation., Results: A total of 310 patients with NSCLC were screened for genetic mutations. Of these, 281 (91%) had adenocarcinoma, 207 (66%) were born in Reunion Island, 79 (25%) were never-smokers, and 109 (35%) were women. One hundred and seventy-eight (57%) patients had a genetic mutation. An EGFR mutation was detected in 69 patients (22%) of the 310 included patients. This mutation was detected in 23% of patients with adenocarcinoma, 40% of women, 55% of never-smokers, and 23% of patients born in Reunion Island., Conclusion: The frequency of EGFR mutation is high in the Reunionese population. This frequency is similar to that reported in Asia and may be explained by the history of migrations and ethnic mixing in Reunion Island. These findings suggest complex interactions between genetic and environmental factors in the carcinogenesis of NSCLC., Competing Interests: Declarations of Competing Interest None., (Copyright © 2022. Published by Elsevier Masson SAS.)