Herein, we report a 55-year-old male patient with stage IV NSCLC harboring a rare EGFR L833F-L861Q compound mutation in cis....Upon disease progression, the heavily pretreated patient was treated with osimertinib and bevacizumab, and both lung lesion and brain metastases were stable for more than 3 mo. He had an overall survival of 25 mo. Our case revealed that both afatinib and the osimertinib + bevacizumab combination demonstrated clinical efficacy in NSCLC harboring an EGFR L833F-L861Q compound mutation.