Cronkhite–Canada syndrome (CCS) is a rare nonhereditary disorder characterized by multiple gastrointestinal polyps and ectodermal changes. The mortality rate can reach up to 50% in patients with delayed diagnosis or inadequate treatment. A 78-year-old Japanese woman presented with diarrhea as the primary complaint. Her clinical presentation included diarrhea, dysgeusia, anorexia, and weight loss. Physical examination revealed alopecia, nail atrophy, and hyperpigmentation. Abdominal computed tomography (CT) revealed multiple enlarged mesenteric lymph nodes, whereas endoscopic examination showed numerous hyperplastic polyps extending from the stomach to the colon. Following the diagnosis of CCS, the patient was treated with prednisolone (30 mg/day). Abdominal CT imaging one month later showed a reduction in the mesenteric lymph node size. Although it is uncommon, mesenteric lymphadenopathy can appear in CCS and may regress with corticosteroid therapy.