Objective To examine epidermal growth factor receptor (EGFR) gene mutations in small bronchoscopic biopsy specimens, so as to provide guidance for clinical targeted therapy. Methods Fifty-six female patients with advanced-stage ⅢB-Ⅳ lung adenocarcinoma underwent endoscopic endobronchial biopsy of tumor tissues or transbronchial needle aspiration of mediastinal and hilar lymph nodes. Under the endoscope, 20 patients underwent only bronchial biopsy, 28 underwent only transbronchial needle aspiration (TBNA) lymph node biopsy, and 8 underwent both endobronchial biopsy and TBNA biopsy of mediastinal and hilar lymph nodes. A total of 64 specimens were collected and were subjected to detection of EGFR gene mutations after confirmation of lung adenocarcinoma. The specimens were then divided into endobronchial metastasis group and lymph node metastasis group, and the mutations of exons 19 and 21 were detected and the clinical efficacy of targeted therapy was analyzed. Results Exon 19 had higher positive rate in the endobronchial metastasis group (χ²=4.304,P=0.038), and exon 21 had higher positive rate in lymph node metastasis group (χ²=18.727,P=0.000). A total of 24 cases were included for the clinical efficacy assessments: 10 had endobronchial metastasis (exon 19 mutations in 8 cases, 21 exon in 2 cases), with the disease control rate being 90% (9/10) and median progression-free survival period being 14.8 months; 14 patients had lymph node metastasis (19 exon 3 cases, 21 exon 11 cases), with the disease control rate being 78.57% (11/14) and the median progression-free survival period being 9.2 months; the disease control rates were not significantly different between the two groups (P>0.05) and the median progression-free survival periods were significantly different between the two groups(χ² = 4.134, P=0.042). Conclusion Mutations of different EGFR exons might relate to the metastasis forms of female advanced lung adenocarcinoma, with exon 19 prone to endobronchial metastasis and exon 21 to lymph node metastasis. Targeted therapy for patients with endobronchial metastasis has a better outcome than that for patients with lymph node metastasis.