A 53-year-old woman was admitted to the hospital because of chest tightness, shortness of breath, and cough for 1 week, and the left lung was occupied for 4 days. Computed tomography (CT) examination revealed left lung occupying. The patient underwent left lung mass puncture with CT guided. Combined with systemic examination, a clear diagnosis of advanced lung adenocarcinoma with epidermal growth factor receptor 19 exon deletion was made. After multi-line chemotherapy, multi-line targeted therapy, and combined therapy, the patient’s treatment process was more frequent. Obtained partial remission (PR) for several times, and made further progress. After the progress, T790M gene tests were performed on different samples and different methods. The test results were significantly different before and after. T790M gene mutations were eventually detected, the patients obtained the treatment of three-generation oral epidermal growth factor-tyrosine kinase inhibitor (EGFR-KTI), and obtained high-quality long-term survival, combination after resistence of three-generation EGFR-KTI further increased the survival benefit of patients.