A 66-year-old man was referred to our hospital for evaluation of fever and right pleural effusion. Laboratory investigations showed elevated serum C-reactive protein levels, thrombocytopenia, procalcitonin positivity, and renal impairment. The patient had exudative pleural effusion, which predominantly showed histiocytes, complicated by disseminated intravascular coagulation, and remained refractory to antibiotics. We observed mild swelling of the cervical, axillary, and abdominal para-aortic lymph nodes, exacerbation of renal impairment, pleural effusion and ascites, and anasarca. Histopathological evaluation of a bone marrow biopsy specimen revealed reticulin fibrosis and megakaryocytosis, which led to the diagnosis of thrombocytopenia, anasarca, fever, myelofibrosis, renal insufficiency, and organomegaly (TAFRO) syndrome. TAFRO syndrome should be considered in the differential diagnosis of patients with pleuritis of unknown etiology.