Dasatinib-related pleural effusion has a relationship with the development of large granulocyte lymphocytosis and complete molecular response in CML patients. Here we present a CML case that was treated with various TKIs and suffered from massive life-threatening pleural effusion and large granular lymphocytosis observed in his blood film. 52 years old male patient who was diagnosed as CML in 2008, first time suffered from dyspnea in January 2014. Chest film revealed bilateral pleural effusion which was considered to be side-effect of dasatinib treatment. In his blood film, a few large granular lymphocytes were present. We have given nilotinib 2x400 mg instead of dasatinib. In August 2015, he had dyspnea and on chest film, again bilateral pleural effusion was observed. He was under full cytogenetic and molecular remission. Our patient has progressive intractable pleural effusion during hospitalization. Two pigtail catheters were placed. In January 2016 pleurodesis was performed. He is still under close control without any TKI treatment. The clonal expansion of large granular lymphocytes in patients who were given dasatinib has been shown to be related with pleural effusion and improved outcome. Nearly for 3 months without any TKI treatment, our patient remained under complete remission. This finding in our patient could be a sign of good prognosis since pleural effusion and large granular lymphocytosis related with improved outcome in CML patient. To conclude, in CML patients the pleural effusion could be resistant and life-threatening adverse effect of TKIs however the existence of large granular lymphocytosis may indicate better prognosis.