PURPOSE: to assess TP53 changes in patients with oral lesions presumed to be malignant or malignant from oral mucosa samples. METHODS: Male-female, 23-84 years old, attended at the Clinical Office of Stomatological Clinic "A", (Faculty of Dentistry, National University of Cordoba, Argentina) in 2009-2010. The lesions were Oral Leukoplakia (OL); n=4, Oral Lichen Planus (OLP); n=6 and Oral Squamous Cell Carcinomas (OSCC), n=10; all lesions were diagnosed by anatomopathological criteria. DNA was extracted according to protocol of Brunotto et al., 2006. Cells were collected from the brushing of lesion and primers were designed in order to amplify the 5-8 exons-introns of TP53 human gene (GeneBank: NC_000017). RESULTS: The patients with OC presented a 35% familiar inheritance and 15% TP53 mutations. In the patients with OL, OLP and OC were observed an average 50% with smoking and drinking habits. The patients with OC presented a 35% familiar inheritance and 15% TP53 mutations. A high percentage of TP53 GC → TA transversion mutations (60%) were observed in all studied lesions. It was observed association between percentage of patients with different type of mutation and different kind of lesions (p-value <0.0001). CONCLUSION: we observed TP53 mutations in OL-OPL (10%) and OC (15%). Our study did not allow us to establish an accurate cause of OL-OLP become to malignancy; the presence of mutations is one indicative characteristic necessary for a patient to be deemed at-risk and incorporated into a monitoring program.