Background: Lung cancer remains the leading cause of cancer-related mortality worldwide, accounting for approximately 1.8 million deaths annually and representing 18% of all cancer deaths¹. According to the GLOBOCAN 2024 report, 2.4 million new cases were registered globally, ranking second after breast cancer². Non-small cell lung cancer (NSCLC) constitutes 85% of lung cancer cases, with adenocarcinoma being the most common subtype³. The objective of this study is to map the prevalence of HER2 activation and mutations in EGFR, EML4-ALK, ROS1, BRAF, and KRAS genes among lung cancer patients in Mongolia, and to evaluate their correlations with clinical and morphological parameters (age, sex, smoking status, stage, and morphology). Aim: To determine the distribution pattern of HER2 activation and EGFR, EML-ALK, ROS1, BRAF, KRAS gene mutations among patients with lung cancer in Mongolia, and to evaluate their associations with clinical and morphological characteristics. Materials and Methods: A retrospective study was conducted using archived materials from lung cancer patients at the Clinical Pathology, Molecular Genetics, and Pathology Laboratories of the National Cancer Center of Mongolia, covering the period from 2019 to June 2025. DNA Extraction from Tumor Tissue: Formalin-fixed paraffin-embedded (FFPE) tissue blocks from patients diagnosed with lung cancer, stored in the pathology department archives, were selected for the study. Sections of 5–10 μm thickness were cut, mounted on glass slides, stained with hematoxylin and eosin (H&E), and reviewed by a pathologist. Areas containing ≥20–30% tumor cells were identified and macro-dissected for analysis. Real-Time PCR Assay for Detection of EGFR/BRAF/KRAS/EML4-ALK/ROS1 Mutations: EGFR mutation detection was performed using the PANAMutyper™ EGFR Mutation Detection Kit (Panagene, Daejeon, South Korea) according to the manufacturer’s instructions. PCR reactions were carried out on a compatible instrument (Roche LightCycler 480, Germany) as recommended by the manufacturer. Statistical analysis was performed using Prisma-10 software. Results: A total of 282 lung cancer cases were included in the study. EGFR mutations were detected in 44% of cases and were absent in 56%. No significant age-related differences were observed (p=0.2636); however, EGFR mutations were significantly more frequent in females (36.6% vs. 19.6%, p=0.0019). No statistically significant differences were found across disease stage, T, N, or M classifications (p>0.05). No association was identified between smoking status and EGFR mutations (p=0.4178). Morphologically, EGFR mutations were significantly more prevalent in adenocarcinoma (54.83%) compared to squamous cell carcinoma (SCC) (31.8%; p=0.002). Of the 282 cases, adenocarcinoma accounted for 155 (54.9%) and SCC for 116 (41.1%). Overall, EGFR mutations were positive in 43.97% of cases, with a higher prevalence in adenocarcinoma (24.82%) than in SCC (13.1%). By exon: - Exon 18 mutations were detected in 6% of cases, predominantly in adenocarcinoma (6%, 4.25%). - Exon 19 mutations occurred in 8.15% and are associated with sensitivity to targeted therapy. - Exon 20 mutations were found in 3.19%, with the T790M resistance variant in 1.77%. - Exon 21 mutations were observed in 9.57%, more common in adenocarcinoma (9.57%) than in SCC (3.19%). Survival analysis stratified by stage at diagnosis showed significantly longer median survival in early-stage patients (18.6 months). Kaplan-Meier curve comparison, log-rank test, and hazard ratio calculations confirmed statistically significant differences (p < 0.05), indicating that disease stage is a key prognostic factor. Conclusion The study findings reveal a high prevalence of EGFR mutations among Mongolian patients with lung adenocarcinoma, underscoring the need for widespread implementation of targeted therapy (EGFR-TKIs). In contrast, mutation rates were lower in SCC and other morphological subtypes, highlighting the importance of investigating alternative molecular markers in these subgroups.