This study evaluated the immunohistochemical expression of claudin-1 and claudin-3 in the most common odontogenic lesions namely RC, OKC, UAB and AB. Comparing the expression levels of these two markers among those lesions and finally, correlation of the obtained results with their biological behaviors were also performed. Forty archival cases of RC, OKC, UAB and AB (10 cases each) were stained with hematoxylin and eosin for histological examination. Streptavidin-biotin method was used for immunohistochemical staining by anti claudin-1 and anti claudin-3 antibodies.For immunohistochemical evaluation, the stained sections were examined by ordinary light microscope. The area percentage of the positive membranous and cytoplasmic claudin-1 and claudin-3 immunoreactions were assessed by the image analyzer computer system using the software Leica Qwin 500. All the obtained data were statistically evaluated. Comparisons among the experimental groups were done using analysis of variance (ANOVA) followed by multiple comparisons post hoc test. Correlations between quantitative variables were done using Pearson correlation coefficient. P-values <0.05 and p-values <0.001 were considered to be significant and highly significant, respectively.Our results revealed variable degrees of claudin-1 and claudin-3 immunoexpression in all the studied cases. Where, the expression level of both markers was gradually decreased starting from RC to OKC, UAB until reaching its lowest value in AB. The statistical analysis of the current work revealed a highly significant difference in area percentage of both markers among the examined groups. In addition, the area percentage of claudin-1 immunoexpression was much higher than that of claudin-3, and the correlation between both markers was positive. Finally, it seems reasonable that claudins-1 and -3 could be useful prognostic biomarkers in odontogenic lesions. However, claudin-1 is more specific for odontogenic lesions than claudin-3. Besides, they could aid in differentiation of the neoplastic from non-neoplastic odontogenic lesions and could be auxiliary indicators of aggressiveness and invasion potentials. However, further studies are recommended to evaluate our results and elucidate the role of claudins in pathogenesis, behavior and prognosis of odontogenic lesions.