We report a case of lung adenocarcinoma with bone metastasis. After multiple line treatments, the blood carcinoembryonic antigen (CEA) increased gradually. The first-generation EGFR-TKI showed resistance in about one year. EGFR T790M mutation was confirmed by Blood test (after 16+ months of Iressa treatment) and second tissue biopsy (after 22+ months of Iressa treatment). In July 2018, after the first use of Osimertinib (80 mg, 1 time/d), platelet decreased significantly, platelet recovered after withdrawal of Osimertinib, thrombocytopenia continued to occur again after Osimertinib treatment. During this period, blood CEA decreased and the lesion was stable, suggesting that Osimertinib treatment was effective, but platelet reduction could not be tolerated until 2018. Osimertinib was discontinued in November 2018. By March 2019, the patient’s condition had progressed significantly and the clinical diagnosis was “meningeal metastasis”, the platelet count dropped from 97×10⁹/L to 37×10⁹/L only three days after the application of osimertinib (80 mg, 1 time/d). The platelet count increased to 68×109/L after the discontinuation of Osimertinib. The reduction of osimertinib to 40 mg (1 time/d) was considered in April 4, 2019, but the platelet count was only 21×10⁹/L in April 8, 2019, and the oral dose of osimertinib was discontinued again. Looking back at this case, if we can switch to osimertinib treatment in time when the tumor load is relatively small (about 1 year of Iressa treatment), we can expect better outcomes. This also reflects that the formulation of treatment plan in the real world is affected by many factors, and it is more and more important to conduct a timely second biopsy to understand the genetic status of patients.