Topical 5-fluorouracil is a common treatment for actinic keratoses. Its side effects may include intense erythema, erosions, contact dermatitis, systemic intolerance in susceptible individuals, and ulcerations. We present a case of a 78-year-old woman who developed unilateral ectropion after topical 5-fluorouracil application. This case highlights the importance of clear patient instruction while prescribing topical 5-fluorouracil. Patients should be advised to wash their hands thoroughly after application. We also stress the importance of counseling patients to keep the medication away from the orbital rim, eye, and eyelid.