Investigation of cyclooxygenase (COX)-2 in dentigerous cyst and ameloblastoma may help to improve understanding of the nature and behavior of odontogenic cysts and tumors, and in addition may eventually represent a definitive target for a pharmacological approach in the management of these lesions. The aim of this study was to evaluate COX-2 expression and its correlation with the proliferation of odontogenic epithelium in these lesions. Dentigerous cysts (n=16) and ameloblastomas (n=17) were evaluated. Detection of Ki-67 and COX-2 protein expression was conducted by immunohistochemistry. Data were statistically analyzed using Mann-Whitney U test and Spearman's rank correlation coefficient. No significant differences were found in the expression of Ki-67 and COX-2 between dentigerous cysts and ameloblastomas (P>0.05). A significant positive correlation (P=0.018) and highly significant positive correlation (P=0.004) were found between Ki-67 and COX-2 expression in the odontogenic epithelium of dentigerous cyst and ameloblastoma, respectively. COX-2 was expressed in the odontogenic epithelium of dentigerous cyst and ameloblastoma. It may contribute to local extension of these lesions by increasing the proliferation of their odontogenic epithelial cells.