Introduction: The 5-fluorouracil (5-FU) discloses a cure rate greater than 90 percent in potentially malignant lesions of skin. In the oral cavity, these lesions are treat in most cases with practice surgery, which reduces the number of patient involvement by malignant lesions, not being usual treatment with chemotherapeutic drugs. The aim of this study was to evaluate the effectiveness of the antineoplastic agent 5-fluorouracil in orabase ? in potentially malignant lesions of the lingual mucosa in mice. Materials and Methods: Swiss albino mice (Mus musculus) were submitted to carcinogen 4-nitroquinoline-1-oxide (4NQO), 100 ?g/ml in drinking water for 8 weeks, and on developing potentially malignant lesions on the tongue, were treated daily, with topical 5-FU in orabase ? at concentrations of 0.5% and 5%, for 3 weeks. The tongues were processed for analysis by light microscopy. Results: Treatment with 5-FU in orabase ? was shown to be effective in the histological degree of involution of the epithelial lesions of the tongue in the treated animals (p<0.05). However, when compared, there was no statistically significant difference between the two concentrations (p>0.05). Conclusions: The 5-FU in orabase ? was shown to be a feasible therapy in potentially malignant lesions of the oral cavity.