Abstract: Background and Objective: Odontogenic tumors comprise a complex group of lesions which can pretense diagnostic challenges because of overlapping and diverse histopathologic types and clinical behaviors. An understanding of the biological behavior of these lesions is of fundamental importance for the final diagnosis and treatment planning, as these have an influence on the prognosis. The goal of the present study was to analyze and correlate the immunohistochemical expression of NF-κB and its transcription targets Bcl-xL and COX-2 in different odontogenic tumors. Materials and Methods: Thirty paraffin blocks of different odontogenic tumors (six dentigerous cyst, fourteen simple ameloblastoma, five unicystic ameloblastoma and five ameloblastic carcinoma) were selected. Immunohistochemistry was performed using the standard method (Avidin biotin peroxidase) to detect the polyclonal anti-NF-κB, Bcl-xL and COX-2 antibodies. One-way ANOVA and Spearman correlation test was used for statistical analyses. Results: The overall expression of the three antibodies (NF-κB, Bcl-xL and COX-2) increased significantly (p-value was considered significant when p<0.05) from dentigerous cyst to ameloblastoma and reached their highest values in the cases of ameloblastic carcinoma. Conclusion: The interaction between the three proteins in blocking apoptosis and increasing proliferation may constitute an important pathogenic mechanism of tumorigenesis and hence might play a role in the behavior of odontogenic tumors.