A variety of cutaneous reactions have been reported with the use of systemic 5-fluorouracil. Our patient had serpentine hyperpigmented streaks appearing 5 days after bolus infusion of 5-fluorouracil. The patient also had other skin eruptions, that is, inflammation of actinic keratoses and folliculitis limited to the forehead; these reactions have been reported previously with 5-fluorouracil medication. We report this case and review the literature on skin manifestations associated with 5-fluorouracil therapy.