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McKittrick-Wheelock Syndrome is a rare disorder, noted for electrolyte and fluid depletion caused by secretory colorectal adenomas and carcinomas. We report here the first reported case of a 55-year-old man with a large rectal villous adenoma coexistent with a poorly differentiated neuroendocrine tumor of rectum presenting with McKittrick-Wheelock Syndrome. Palliative chemotherapy resulted in complete resolution of symptoms and improved quality of life.