A patient with stage IV epidermal growth factor receptor (EGFR)-positive lung adenocarcinoma admitted to the First Affiliated Hospital of Zhengzhou University demonstrated that multiple biopsy and local treatment played an important role in the treatment. The patient, female, 76 years old, came to our hospital for complaints in February 2017 because of “continuous back pain for more than 1 month and found left lung mass for 1 week”. PET-CT examination in the external hospital suggested that the left upper lobe occupied the metabolism of the upper lobe. Considering lung cancer, the T11, T12 and L2 vertebral bodies were active and metastatic. Lung biopsy, puncture pathology showed: lung adenocarcinoma, EGFR 19 exon deletion mutation. The diagnosis was “left lung adenocarcinoma cT2aN0M1c IVB phase”. First-line treatment: “targeted therapy + topical treatment” (gefitinib + vertebral metastases microwave ablation and vertebroplasty + zoledronic acid), Progression-free survival (PFS) for 8 months. In October 2017, local disease progressed, and a biopsy was performed again. The pathology showed: lung adenocarcinoma, EGFR exon 19 deletion mutation. Treatment plan: “targeted therapy + topical treatment” (gefitinib + left lung cancer radiofrequency ablation), PFS for 4 months. In February 2018, the disease progressed rapidly, and the third puncture biopsy targeted new metastasis of the lung. The pathology showed: lung adenocarcinoma, EGFR exon 19 deletion mutation. EGFR 20exon T790M missense mutation. Second-line treatment: targeted drug (oheptinib mesylate), PFS for 18 months. In August 2019, the disease progressed rapidly, with multiple nodules in the lungs and multiple nodules in the brain. The fourth biopsy path showed: EGFR exon 19 deletion mutation. EGFR exon 20 T790M missense mutation. Three-line treatment regimen: chemotherapy (pemetrexed + lobaplatin + recombinant human endostatin) 2 cycles. The patient is still in follow-up.