In early-stage non-small cell lung cancer (NSCLC), the recommended treatment options include targeted and immune therapies. However, there’s a lack of comprehensive biomarker prevalence data for Latin America (LATAM). The EARLY-EGFR study, conducted across Asia, the Middle East, Africa, and LATAM, aimed to determine the frequency of EGFR mutations (EGFRm) in patients with surgically resected stage I-III non-squamous NSCLC. The LATAM subset of this real-world, observational study prospectively enrolled consecutive patients with surgically-resected stage IA-IIIB non-squamous NSCLC from March 2021 to October 2022. The primary endpoint was to assess EGFRm prevalence, with secondary objectives including evaluating EGFRm subtypes, patient demographics, and treatment patterns. The association between EGFRm and patient demographics was analyzed using Fisher’s exact test with Monte Carlo simulations. A total of 80 patients were enrolled, with an average age of 66.5 years. 67.5% of the patients were female, and 57.5% were never smokers. All patients had adenocarcinoma, with the majority falling into pathological stage (PS) I (66.3%), followed by PS II (20.0%) and PS III (13.8%). Most cases (61.3%) involved the right lung, and 85.0% were node-negative (pN0). EGFRm prevalence was observed in 39.5% of cases, with similar rates in both male and female patients. The two most common EGFRm subtypes were exon-19 deletions (36.7%) and 21-L858R mutations (30.0%), accounting for two-thirds of all mutations. Notably, 36.4% of EGFRm-positive patients were also found to be positive for PD-L1. The EGFRm rate was significantly higher in never smokers compared to current and former smokers (51.2% vs. 24.2%, p=0.017). About 76.3% of patients underwent surgical resection alone, and only around 32% of patients with PS IB-IIIB received systemic adjuvant therapy, primarily platinum-based chemotherapy. Logistic regression analysis revealed that patients aged 60 and above had increased odds of having EGFRm, while smokers had decreased odds (both p<0.05). The findings from the LATAM subset demonstrate an EGFRm prevalence of 39.5%. Despite ASCO guidelines recommending adjuvant therapy for patients with PS IB-IIIB, only a minority received it. These results provide crucial insights for guiding EGFR testing and treatment strategies in LATAM, particularly in light of recent and forthcoming approvals of targeted and immune therapies.