Odontogenic keratocyst is a generally asymptomatic intraosseous lesion, commonly located in the posterior mandibular region. It is the third most prevalent cyst in the oral cavity and the most studied currently due to its aggressive behavior and high recurrence rate. To reduce the rate of lesion recurrence, the use of topical 5-fluorouracil has been proposed as an alternative adjuvant treatment to enucleation due to the success rate demonstrated in basal cell carcinomas, an entity whose molecular pathogenesis is similar to that of odontogenic keratocyst. The case of a 54-year-old patient with an intraosseous lesion located in the right mandibular ramus is presented, which was diagnosed as a recurrent odontogenic keratocyst and whose treatment was through surgical enucleation and application of topical 5-fluorouracil 5% to through packed gauze for 24 hours. There has been no recurrence of the lesion after 14 months of follow-up.