Giant tubular-villous adenoma of the rectum can determine secretory diarrhea, associated with a depleting syndrome of prerenal acute renal failure, hyponatremia, hypokalemia and hypoproteinemia. These symptoms are known as the McKittrick-Wheelock syndrome, and there are about 50 cases reported in literature. We present the case of a 59-year-old woman presented to our emergency department with abdominal pain, prerenal azotemia, and electrolyte disturbances with a background of chronic diarrhea, caused by a giant rectal tumor. Conservative therapy initially improved and normalized renal function, and made surgical resection of the tumor possible.