A 72-year-old man was referred to our hospital because of bilateral pleural effusion. Although examination of pleural effusion obtained by thoracentesis did not show any specific etiology, we diagnosed yellow nail syndrome due to his yellow nails and lymphedema of both lower limbs. Diuretics were effective for the control of his pleural effusion. Subsequently, fibrosarcoma was found in his abdominal skin and was resected. The pleural effusion gradually increased after the cessation of oral diuretics. Histological examination of a pleural biopsy specimen obtained by thoracoscopy showed chronic lymphocytic inflammation, but no malignancy. His previously intractable right pleural effusion was successfully treated with pleurodesis using OK-432, suggesting that pleurodesis with OK-432 could be an effective method for the control of pleural fluid in this disease.