Statement of the Problem: Considering the clinical differences between central giant cell granulomas (CGCGs) and peripheral giant cell granulomas (CGCGs) despite their same microscopic feature and possible role of angiogenesis in this issue, Purpose: The aim of the present study was to compare microvessel density (MVD) between CGCGs and PGCGs of the oral cavity using CD31 and CD34.Materials and Method: Immunohistochemical staining was performed on 18 PGCGs and 19 CGCGs using a monoclonal antibody against CD34 and CD31. MVD was assessed and compared between the lesions using T-test for statistical analysis. p< 0.05 was considered significant.Results: The expression levels of both CD34 and CD31 were significantly higher in CGCGs compared to PGCGs (p< 0.002 and p< 0.001, respectively). Significant differences in MVD assessed by both markers were observed between males and females in PGCGs (p< 0.05), but not CGCGs (p< 0.2).Conclusion: The combined evaluation of old- and newly-formed vessels by pan-endothelial cell markers showed differences between CGCGs and PGCGs, supporting the possible vascular-proliferative nature of the former. Whether this difference has a part in their diverse biologic behaviors and the role which pre-existent vessels play in comparison to neo-formed vasculature, requires further investigation.