Objectives: To evaluate the effectiveness of Toki's criteria in identifying the HPV L1 protein in oral lesions with the use of immunohistochemistry (IHC) and to determine which criteria optimize such identification.Study Design: Retrospective study of 277 cases diagnosed as HPV lesions at 22 years.Tests of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), kappa coefficients, and chi 2 values, as well as two logistic regression analyses (p≤0.05), were conducted.Results: Of the lesions studied, 96.4% (267 of 277) were positive for HPV using Toki's criteria and 28.5% (79 of 277) were positive for L1 by IHC.Toki's criteria showed sensitivity=93.67%,specificity=2.53%,PPV=6.99%, and NPV=46.55%.Neither concordance nor statistically significant associations were observed between both tests.The logistic regression of Toki's criteria was useful in the diagnosis of L1, correctly classified 71.8% of the lesions positive for L1, and showed a Hosmer-Lemeshow adjustment of p=0.614 and a Nagelkerke's coefficient of determination of 6.8%.The explanatory variables statistically significant at p≤0.05 were dyskeratosis (p=0.01) and papillomatosis (p=0.04).Forty-nine independent variables (clinical and histopathologic) were involved in the second regression analysis.The model correctly classified 85.2% of the lesions and showed a Hosmer-Lemeshow adjustment of p=0.696 and a Nagelkerke's coefficient of determination of 60.2%.The explanatory variables statistically significant at p≤0.05 were: age younger than 35 years (p=0.001),multiple lesions (p=0.031),hyperorthokeratosis (p=0.019),focal intracellular edema (p=0.002), and the presence of 1 to more than 5 cells with degenerative changes in their nucleus (p=0.048).e539 Conclusions: Toki's criteria are not adequate to make a diagnosis of lesions by HPV in the mouth, but the logistic regression analysis showed clinical and histopathologic variables which optimize the identification of lesions through the L1 protein.However, a PCR study is advisable when the presence of high-risk HPV is suspected.