Abstract: Objective To explore the clinical characteristics of patients with bilateral malignant transudative pleural effusion as main manifestation. Methods One multiple myeloma (MM) patient with bilateral pleural effusion as main manifestation was treated in Chinese PLA General Hospital. The clinical characteristics of the patient were retrospectively analyzed and its related literatures were reviewed. Results The patient was a 49-year-old man. Before admitting to our hospital, he went to many other hospitals. Due to his main symptom being dyspnea after exercise resulting from bilateral transudative pleural effusions for more than one year without anemia, bone disease, renal insufficiency and calcium elevation, it was considered as a benign disease and etiology could not be found. The patient had undergone anti-infection and antiphthisic therapy without any efficacy, and his pleural effusion was drained 1 500-3 000 ml a day by himself. On admission, laboratory tests revealed transudative pleural effusion. Protein electrophoresis of serum was positive for IgG-LAM, which suggested plasma cell disease. Plasma cells proportion was 4.8% on bone marrow smear with immature morphology. Flow cytometry of BM specimen showed a clonal population of plasma cells (5.31%), but no symptoms of myeloma were shown in this patient and his symptoms did not met with the diagnostic criterion of active multiple myeloma. Flow cytometry of pleural effusion exhibited a clonal population of myeloma cells, comprising 49.99% of ANC in pleural effusion. The patient was definitively diagnosed with MM. Conclusion Multiple myeloma with bilateral transudative pleural effusion as an initial manifestation is rare, which will be misdiagnosed easily. Flow cytometry of pleural effusion is very useful for diagnosing MM with pleural effusion.