Cronkhite-Canada syndrome is a rare form of nonhereditary gastrointestinal polyposis associated with ectodermal change and protein-losing enteropathy. Here we report a 63-year-old male presenting with diffuse gastrointestinal polyposis, onychodystrophy, cutaneous pigmentation, alopecia, diarrhea, hypoalbuminemia and lower leg edema. Technetium-99m-labeled human serum albumin scan confirmed the patient to have protein-losing enteropathy, which originated from the transverse and descending colon. Subtotal colectomy was performed. Albumin level and ectodermal change were gradually improved during three years of outpatient clinic follow-up. Based on our finding, Technetium-99m-labeled human serum albumin scintigraphy is helpful to localize the protein-losing origins and surgery is an effective treatment for Cronkhite-Canada syndrome with protein-losing enteropathy.