Objectives: The aim of the present work is to study the immunoexpression of the proliferation marker IPO-38 in odontogenic Keratocyst (OKC) and ameloblastoma and compare between them as regards cell proliferation. Materials and methods:A total of thirty specimens were selected in the form of fifteen specimens for each case previously diagnosed as OKC and ameloblastoma. The specimens were submitted to heamatoxylin and eosin staining as well as to immunohistochemical staining by the streptavidin-biotin-peroxidase method and were incubated with IPO-38 antibody.Quantification of the IPO-38 positivity was performed using the image analyzer computer system which measured the area percentage of IPO-38 immunoreactivity. Data obtained from the computer image analysis were tabulated and statistically analyzed (P ≤ 0.05) with Mann-Whitney U test and data were summarized as mean and standard deviations. Result: The results of this work revealed IPO-38 positivity in all cases of odontogenic keratocyst OKC ameloblastoma. Immunoreactivity was detected in the nuclei of these lesions. The mean IPO-38 area percent of OKC was (18.7) and in ameloblastomawas(26). There was no statistically significant difference (P=0.447) of IPO-38 between OKC and ameloblastoma. Conclusion: These findings support previous studies that the evaluations of proliferative activity are useful in predicting the different biological behavior of odontogenic lesions and OKC should be regarded as a benign tumor rather than simply an odontogenic cyst.