INTRODUCTION: Cronkhite Canada syndrome (CCS) is a rare, acquired polyposis syndrome associated with serious complications and a high mortality rate. Awareness regarding presenting symptoms, endoscopic findings, and pathologic features leads to early diagnosis and treatment, and improved survival. CASE DESCRIPTION/METHODS: 68 yo female with a history of alopecia totalis presented with 6 months of non-bloody diarrhea, 30 lb weight loss, and dysgeusia. Physical examination revealed complete alopecia, pitting lower extremity edema, and thinning and splitting of the fingernails. Diagnostic workup yielded marked hypoalbuminemia (albumin 1.1 g/dL), positive SS-a antinuclear antibody (titer 1:160), and elevated serum total IgG level (1,750 mg/dL). CT was notable for a thickened stomach with edematous rugae, and focal segmental colitis involving the cecum and ascending colon. Push enteroscopy showed diffusely edematous mucosa in the gastric antrum and duodenum with denuded appearing vili throughout the small bowel. Colonoscopy revealed diffuse polyposis throughout the entire colon and terminal ileum, with edematous underlying colonic mucosa. Biopsies of affected areas showed diffuse cystic dilation, edema of the lamina propria, and presence of plasma cells, compatible with CCS. The patient was initiated on total parenteral nutrition, prednisone 40 mg daily, and Imuran 75 mg daily. In follow up, she reported complete resolution of dysgeusia, reduction in diarrheal symptoms, weight gain, and improved energy level. Serum albumin level improved to 2.92 g/dL. DISCUSSION: Cronkhite Canada syndrome is a sporadic, acquired polyposis syndrome characterized by diffuse gastrointestinal polyposis and ectodermal features. It carries a 5-year mortality rate of 55% despite therapy, due to a high rate of serious complications, including malabsorption, infection, heart failure, and GI bleeding. Patients are at high risk of gastric and colorectal malignancies (10.4% and 25%, respectively), necessitating annual screening examinations. A combination of nutritional support and immunosuppression with prednisone (tapered dosing) and imuran (2 mg/kg) helps in achieving clinical remission and avoiding relapse. Expedited diagnosis and application of therapy has led to improvement in patient survival and achievement of clinical response. Therefore, improved clinician awareness of disease manifestations, pathologic findings, and treatment regimen is necessary to modify the disease course for this syndrome.