In the present study the combination of p53 over-expression and high Ki67/p53 ratio seemed to better associate with the occurrence of OSCC and severe epithelial dysplasia, and may have a routine implication as an easy method to early detect oral lesions with an impairment of p53 pathway, and probably at risk of developing OSCC. This evidence concerns the gene TP53 and intraepithelial neoplasia.