Hebei General Hospital treated a 51-year-old woman with pleural effusion as the first symptom of lung cancer, positive EGFR mutation, T790M mutation and 7-year history of breast cancer after operation. This woman presented with chest tightness and shortness of breath for one month. A computed tomography (CT) of the chest demonstrates pleural effusion in the right hemithorax. The cytological diagnosis confirmed malignant cells in the pleural effusion with epidermal growth factor receptor (EGFR) exon 19 deletions mutation. Paclitaxel liposome in combination with lobaplatin was administered, with bevacizumab for 3 cycles. Therapeutic effect evaluation was SD. Erlotinib was initiated in December 2017. She remained free of disease progression after 15 months. A T790M mutation was detected in lung biopsy. She was administered Osimertinib from March 2019. She was regularly followed up by the hospital team. Multiple primary cancer is rare. During the treatment, we should pay attention to the second biopsy and implement the concept of precise treatment.