Objective The aim was to examine the relationship between clinicopathological features and immunoexpression of hMLH1 and hMSH2 proteins in pleomorphic adenoma (PA) of minor salivary glands. Study design Paraffin-embedded samples of typically benign PA lesions (n = 35) were prepared for histologic and immunohistochemical assessment. Based on the clinicopathologic features, the samples were categorized into low- and high-risk subtypes for their estimated potential for malignant transformation. Results Immunohistochemical analysis revealed strong correlations regarding the expression estimation and staining-intensity distribution (SID) scores between the two proteins. Although there was no relationship between marker immunoexpression and SID scores regarding clinical parameters, statistically significant variations for these parameters were evident regarding some histologic criteria or for risk stratification subtypes. Conclusion The findings of this study could suggest the relationship of a DNA mismatch repair deficiency with high-risk subtypes of PA and the implication of its role in the origin and progression of these subtypes.