POEMS syndrome is a rare, serious, multisystem disorder and its diagnosis is frequently missed due to its varied clinical presentation. We report here, a 69-year-old woman with initial complaints of distended abdomen, who was misdiagnosed with tuberculosis but failed anti-tuberculosis treatment. Further examinations showed peripheral neuropathy, monoclonal plasma cell disease, sclerotic bone lesions, an elevated serum vascular endothelial growth factor (VEGF) concentration, lymph node hyperplasia, endocrine abnormalities, and skin hyperpigmentation. A diagnosis of POEMS syndrome was made and the patient responded to lenalidomide-based chemotherapy.