Cronkhite-Canada syndrome (CCS) is a very rare disorder with less than 500 reported cases. It is characterized by extensive gastrointestinal polyposis and ectodermal anomalies including alopecia, cutaneous hyperpigmentation, and onychodystrophy. Only 3 cases of associated kidney disease (membranous nephropathy [MN]) have been reported. A 71-year-old male with CCS was referred for further evaluation of proteinuria. The patient initially presented with abdominal discomfort, weight loss, dysgeusia, skin hyperpigmentation, alopecia, and dystrophic nails. Endoscopic evaluation showed widespread gastrointestinal nodular inflammation and polyps. Histopathology was consistent with CCS. Initial treatment was with prednisone, azathioprine, and ranitidine. He had moderate clinical improvement but developed nephrotic-range proteinuria. Renal biopsy showed MN, and cyclosporine was started. The patient had significant improvement in his CCS manifestations; however, his proteinuria and renal function worsened. Rituximab was added to his regimen of cyclosporine and azathioprine, which resulted in remission of his MN, marked improvement in his polyposis, and near resolution of his cutaneous symptoms. This case represents a unique presentation of CCS associated with MN treated with rituximab. The excellent clinical response observed for both CCS and MN advocates consideration of this treatment, especially for refractory disease.