Pleural effusion in chronic myeloid leukemia (CML) has been rarely reported in medical practice. Additionally, the correlation of pleural effusion with blast crisis is unknown. This study reported a 66-year-old male patient who was diagnosed with bilateral pleural effusion three months before the blast transformation. Bilateral pleural effusion spontaneously resolved before the blast transformation. The cause of pleural effusion was unknown. Bilateral pleural effusion caused by unknown or known factors, except for that induced by drugs, is a poor prognostic marker for CML and is an unusual indicator of blast crisis. The presentation of the study case indicates that bilateral pleural effusion is an atypical and discernible early indicator of blast crisis onset in patients with CML.