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Cronkhite-Canada Syndrome (CCS) is a rare, sporadic polyposis condition. The literature on CCS consists mostly of case reports. Although disease presentation has been well-described, there is no consensus on the management of CCS. We present a severe case of CCS that demonstrated clinical and endoscopic response to corticosteroids. This response was maintained with azathioprine. This case provides additional experience on a therapeutic strategy to induce and maintain a durable corticosteroid-free remission.