Objectives: to report the immunoexpression of metallothionein in oral leukoplakia and to correlate with histological grade and clinical localization. Leukoplakia is the most common potentially malignant lesion of the oral cavity. As the histological study of oral leukoplakia can not predict precisely the malignant transformation of this lesion, and metallothionein is a protein that has been associated with carcinogenesis, this study could be auxiliary in this histological assessment of this lesion. Study design: samples of oral leukoplakia (35 cases) and of normal oral mucosa (10 cases) were evaluated. Oral leukoplakia was graded in: hyperkeratosis without dysplasic change (9 cases), mild dysplasia (8 cases), moderated dysplasia (10 cases), and severe dysplasia (8 cases). Immunohistochemistry for the metallothionein was performed and the Mann-Whitney test was used in statistical analysis. Results: metallothionein was identified in squamous cells of the all samples. The metallothionein stain in all cases exhibit a mosaic pattern and was predominantly in compartments cytoplasmatic and nuclear simultaneously. The total stain was significantly higher in moderate dysplasia when compared with normal oral mucosa, hyperkeratosis, and mild dysplasia. Conclusion: it was suggested that the metallothionein may be a marker to moderate dysplasia and may play a role in oral carcinogenesis.