Objective: The current study investigated the expression of MCM3 and CD31 in aggressive versus non-aggressive central giant cell granuloma (CGCG ) Materials and methods: Thirty-three paraffin blocks for CGCG cases were collected from Oral Pathology Departments, Faculty of Dentistry, Mansoura, and Alexandria Universities. The Immunohistochemical staining for CD31 and MCM 3 was performed, assessed, and scored. Results: Mean age of the studied cases was 35.6±9.1 years. The lesions that occurred in the mandible represented the majority of cases [27 cases (81.8%)]. The study revealed an association between aggressiveness and the presence of large swelling, pain, cortical perforation, root resorption, and recurrence where they were significantly higher in group 1 (aggressive cases) than in group 2 (non-aggressive cases). Group 1 revealed histologically numerous MNGCs, more cellular connective tissue Stroma, numerous vascularity, and areas of Hemorrhage. Our study showed a highly statistically significant association between MCM3 expression and size and recurrence of the lesion. Statistically, a significant correlation existed between aggressive cases and MCM3 expression. All aggressive cases were associated with a high reaction of MCM3. Comparisons of size and recurrence of the lesions with CD31 expression revealed a highly significant association with high marker reaction in large-size lesions and recurrent cases. The Association between CD31 expression and the presence of aggressiveness was significant. All aggressive cases were associated with a high reaction of CD31 and showed a significant increase in MVD. MCM3 showed a highly significant positive correlation with CD31. Conclusions: Highly significant correlation existed between cell proliferation represented by MCM3 expression and angiogenesis represented by CD31 expression in CGCGs.