Objective: Metallothionein (MT) may play a preventive role in various carcinogenic process. 4NQO is an alkaline compound and potent mutagen that causes the formation of DNA adducts. The purpose of this study was to evaluate the immunoexpression of MT in palatal cells of mice submitted to the carcinogen 4NQO. Study design: C57BL/6 mice received applications of 4NQO to palate for periods of 8, 16, 20 and 24 weeks (experimental group). A control group received only applications of propylene glycol for the same periods. Subsequently animals of experimental and control groups were sacrificed and the palate was histologically analysed and MT immunohistochemistry performed. Results: Although morphological atypical features were scant, the expression of MT was higher in the experimental group in comparison to controls. There was an amplified induction of MT expression in oral epithelium of mice treated by 4NQO. Conclusion: These results suggest that MT may act as an endogenous defensive factor against 4NQO in early phases of oral carcinogenesis.