Chylothorax results from various causes, such as malignancy, trauma, or infection. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) is a multisystemic syndrome that is associated with plasma cell disorder. Pleural effusion is a common manifestation of POEMS syndrome, but the association of POEMS syndrome with chylothorax has not been reported. We report on a 61-year-old female patient who initially presented with dyspnea and bilateral leg edema. Importantly, the patient had normal renal function. Her chest X-ray and computed tomographic imaging showed bilateral pleural effusion, and her chest drainage revealed chylothorax. Detailed examination failed to reveal the definitive cause of the chylothorax. She received several treatments for chylothorax, namely, a low-fat diet or fasting, total parenteral nutrition, a somatostatin analog (octreotide), thoracic duct ligation by video-assisted thoracic surgery, and pleurodesis. However, further examination revealed endocrinopathy, monoclonal plasma cell disorder, peripheral neuropathy, and elevation of the serum level of vascular endothelial growth factor. The patient’s condition was consequently diagnosed as POEMS syndrome. Eventually, her chylothorax was controlled by pleurodesis, and she was transferred to another hospital for stem cell transplantation. Herein, we report on the apparent first case of POEMS syndrome with chylothorax. In some cases of idiopathic chylothorax, the underlying primary disease may be latent, such as in the present patient. POEMS syndrome is rare, but this syndrome should be included in the differential diagnosis of chylothorax with unexplained etiology.