Samar Soliman Elsaid¹, EssamTaher Gaballa² and Walid Zedan³ 1-Teaching assistant, Department of Oral Pathology, Faculty of Dentistry, Mansoura University, Egypt. 2- Vice dean of Student and Teaching affairs,Professor of  Oral Pathology, Faculty of Dentistry,Mansoura University, Egypt. 3- Dean of faculty of Dentistry, Professor of Oral Pathology, Faculty of Dentistry, Zagazig University, Egypt. Abstract: Background: Paying attention to ameloblastoma and keratocystic odontogenic tumor (KCOT) had rised due to their violent clinical behavior and high recurrence rates. Proliferating cell nuclear antigen (PCNA) is a cell proliferation marker, Receptor activator nuclear factor kappa B (RANK) and RANK ligand has a vital  role in osteoclastogenesis. The today's work aimed to investigate the immunohistochemical results of PCNA in KCOT and ameloblastoma, investigate the immunohistochemical expression of RANK and RANKL in both tumors and correlate the immunohistochemical expression of PCNA, RANK and RANKL in KCOT and ameloblastoma.                                                         Material &methods:Theimmunohistochemical expressions of PCNA, RANK and RANKL were conducted on 40 formalin fixed, paraffin embedded tissue blocks (25 KCOT, 15 ameloblastoma) then The immunoreactivity of PCNA, RANK and RANKL was evaluated by Computer Assisted digital image analysis (Digital morphometric study) and scored according to the statistical percentiles of ameloblastoma group into 4 groups.                                             Results:The statistical analysis revealed that males were more affected than females in KCOT and ameloblastoma with mean age 25.20 ±12.67 in KCOT and 36.27±13.16 in ameloblastoma. The mandible was the most affected site in KCOT and ameloblastoma. Moreover, there was no statistically significant difference between KCOT and ameloblastoma in PCNA, RANK and RANKL expressions.      .                                                                                          Conclusion: The aggressiveness and the biological behavior of KCOT and ameloblastoma could be predicated from the level of PCNA, RANK and RANKL which were nearly similar.