Rationale: Cronkhite-Canada syndrome (CCS) is a rare disease, the etiology of CCS is currently unknown. Although CCS is widely accepted as a benign disorder, the malignant potential of the polyps in CCS patients is yet controversial. Patientconcerns: A 55-year-old Chinese male was first admitted to Beijing Friendship Hospital with a 3-month history of frequent watery diarrhea (10-15times/day), loss of taste, and a weight loss of 10kg in August 2010. The left heel bone fracture in the patient occurred about 2 weeks prior to his diarrhea. Diagnoses: He was diagnosed as Cronkhite-Canada syndrome. Interventions: Oral administration of prednisone was initiated at a dosage of 20 mg/day. Outcomes: After 3 months of treatment, the clinical manifestations disappeared, and colonoscopy showed sparsely distributed small polyps in the colon. Consequently, the dose of prednisone was reduced to 10 mg. However, after 4 months, his fingernails were again found atrophic along with mild abdominal discomfort without diarrhea. Colonoscopy revealed a recurrence of the polyps in March 2011. The treatment was repeated with prednisone at a dosage of 20 mg/day resulting in subsided symptoms. In September 2011, he underwent colonoscopy although no significant clinical manifestations were observed. In addition, the polyp in the sigmoid colon was cancerated. Lessons: The present case indicated that the physical stress was related to CCS and malignant transformation occurred in Cronkhite-Canada syndrome polyp. After the diffused inflammatory polyps have responded to steroid therapy, other existing adenomas require endoscopic treatments, which can decrease the possibility of neoplastic transformation.