A non-smoking 58-year-old female was diagnosed with lung adenocarcinoma (pT2N0M0, according to seventh TNM classification) after right lower lobe lobectomy. A SurPlex™ liquid chip test (SurPlex™-xTAG, Surexam, P.R. China) was performed on the resected tumor tissue, which showed an activated mutation of EGFR exon 19 deletion (19 Del, p.E746_S752>V), no KRAS, BRAF, PIK3CA mutation. The patient was administered with gefitinib at a dose of 250 mg/day for 1 year, during which the patient was stable (according to the Response Evaluation Criteria in Solid Tumors). Gefitinib therapy was discontinued after appearance of liver metastasis in December 2013, and second-line chemotherapy (pemetrexed 850 mg, d1+ cisplatin 40 mg, d1–d3) and percutaneous microwave coagulation therapy of liver were administrated. However, the patient discontinued the chemotherapy after two cycles due to serious adverse effects of nausea and vomiting and continued with gefitinib treatment again. New liver metastases and a pulmonary mass were detected in March 2015. Wedge resection of left upper lobe was carried out by video-assisted thoracoscopic surgery and pathological diagnosis was adenocarcinoma (pT2NxM1, IV stage). Next-generation sequencing (NGS, Langqing™, Burning Rock Dx, P.R. China) of the tumor biopsy presented EGFR 19 Del and T790M mutation, MAP2K1 and TP53 mutation, no ALK and ROS1 mutation. The patient was enrolled in the Phase II clinical trial of osimertinib (40 mg/day) instead of gefitinib therapy. The patient progressed with brain metastasis in June 2015 and withdrew from the clinical trial and changed dose of osimertinib from 40 mg/day to standard 80 mg/day, complementary with stereotactic brain irradiation. The patient developed multiple metastases after several months and the peripheral blood NGS test (Langqing™) showed rare EGFR G724S on 2 June 2016 (in addition to EGFR 19 Del and T790M). Then, the therapy combined osimertinib 80 mg/day and gefitinib 250 mg/day. Moreover, the patient’s family purchased pembrolizumab and cabozantinib (XL184) from outside China, which also failed to slow down the progress of the disease. Two additional peripheral blood NGS tests revealed MET amplification in August and September 2016. However, the disease worsened quickly and the patient died of respiratory failure on 25 September 2016. All the processes of diagnosis and treatment are shown below ( and ).