Rationale: Cronkhite-Canada syndrome (CCS) is a nonhereditary, rare polyposis condition, first documented by Cronkhite and Canada in 1955. The primary distinct features of this syndrome include ectodermal abnormalities and diffuse gastrointestinal polyp changes accompanied by protein loss. The primary clinical manifestations of CCS include hair loss, excessive pigmentation of the skin, and malnourishment of fingernails or toenails. Other notable symptoms include weight loss, protein-losing enteropathy, diarrhea, abdominal pain, nausea, vomiting, taste abnormalities, and atrophic glossitis, which predominantly occur in middle-aged and older males. CCS is characterized by an extremely rare, nonfamilial hamartomatous polyposis syndrome, in which polyps are distributed in the stomach and colon (90%), small intestine(80%), and rectum (67%), while sparing the esophagus., Patient Concerns: This report describes a 72-year-old female, initially treated for intestinal obstruction, followed by a small intestine resection. She reported diarrhea, emaciation, and loss of appetite across various hospitals., Diagnoses: Endoscopic examination of the stomach and colon, plus capsule endoscopy, revealed multiple polyps throughout her gastrointestinal tract, except in the esophagus., Interventions: Treatment included hormones with antiallergic medication, acid-suppressing drugs, salicylates, and nutritional support with zinc sulfate, adding trace elements and amino acids., Outcomes: posttreatment, the patient demonstrated significant improvement in appetite and taste. Atrophic glossitis, upper limb pigmentation, and frequency of diarrhea also notably decreased. reexamination through endoscopy after 3 months of treatment revealed a substantial decrease in the number and size of gastrointestinal polyps., Lessons: In this case, from the lower esophageal sphincter to the rectum, there is an increasing trend of eosinophil and mast cell infiltration. These lesions can cause a positive IgG result. Pathological analysis indicates that the extent and severity of lesions in the middle and lower gastrointestinal tract are more substantial than in the upper tract. During treatment, endoscopic observations reveal that lesions in the middle and lower tract tend to resolve faster than those in the upper tract. Hormone therapy has demonstrated significant efficacy in treating this disease. Early treatment and regular follow-up for this disease can reduce the risk of cancerous changes and related complications., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)