Background: Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer cases and remains one of the leading causes of cancer-related mortality worldwide. Advances in molecular oncology have shown that mutations in the epidermal growth factor receptor (EGFR) gene play a crucial role in diagnosis and in guiding targeted therapy with tyrosine kinase inhibitors (TKIs). However, the detection of EGFR mutations is influenced by specimen type and quality, and differences may exist between bronchoscopic and surgical samples. In Mongolia, studies addressing this issue remain limited. Aim: To evaluate the feasibility of detecting EGFR gene mutations in bronchoscopic and surgically obtained tissue samples from patients with non-small cell lung cancer (NSCLC). Materials and Methods: This prospective comparative study included 35 formalin-fixed, paraffin-embedded (FFPE) tissue samples, of which 19 were bronchoscopic and 16 were surgical specimens. Tumor cell content was assessed histologically, and genomic DNA was extracted from each sample. EGFR mutation analysis was performed using the cobas® EGFR Mutation Test v2 with real-time PCR. Statistical analysis was conducted using SPSS version 26.0, and differences between groups were evaluated using Fisher’s exact test. Results: The mean age of the participants was 64.5±10.5 years; 74% were male and 26% were female. Significant differences in tumor cell content and DNA yield were observed between specimen types. Bronchoscopic samples showed a mean tumor cell content of 34%, with sufficient DNA yield in 73.6% of cases, whereas surgical specimens demonstrated a mean tumor cell content of 93%, with adequate DNA yield in all cases. EGFR mutations were detected in 31.3% of surgical specimens (including exon 19 deletion, L858R, and T790M mutations). In bronchoscopic samples, insufficient DNA yield in some cases precluded PCR analysis, thereby limiting mutation detection. A statistically significant difference in EGFR mutation detection rates was observed between the two groups (p=0.045). Conclusions 1. Bronchoscopic samples demonstrated lower tumor cell content and DNA yield, which may limit their suitability for molecular analysis in some cases. 2. Compared to bronchoscopic samples, surgically obtained specimens provided higher-quality tissue and demonstrated a greater feasibility for EGFR mutation detection.