An 82-year-old man presented with a left eye elevated single ocular surface squamous neoplasia. The tumor involved 360° of limbus, three quadrants of cornea and conjunctiva; this was compatible with the diagnosis of giant ocular surface squamous neoplasia. Topical 5-fluorouracil 1% was planned four times daily for 1 week followed by 3 weeks off-treatment. Patient inadvertently continued 5-fluorouracil, four times daily for 4 weeks, presenting with clinical resolution of the ocular surface squamous neoplasia and subtotal corneal epithelial defect associated with 5-fluorouracil toxicity. One month later, we observed a transparent cornea and no signs of toxicity. Total tumor resolution was observed for at least 6 months of follow-up.