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Wernicke’s syndrome, caused by thiamine deficiency, is most commonly associated with alcoholism but can also occur in patients who are malnourished or have malabsorption of nutrients for other reasons. Since the classic triad of encephalopathy, nystagmus and ataxia occurs simultaneously in only 10–33% of cases, a high index of suspicion is needed in any patient with confusion and memory loss. In this case report, we present a 56-year-old female patient with metastatic colon cancer complicated with enterocutaneous fistula. She developed Wernicke’s encephalopathy precipitated by 5-fluorouracil infusion. Replacement with thiamine rapidly reversed her neurologic symptoms and signs.