The objective of this study was to assess angiogenic activity by analyzing anti-CD105 and anti-CD34 immunostaining in 20 cases of vascular malformations (VMs) and 20 cases of oral pyogenic granulomas (OPG). In addition, the usefulness of these markers for the differential diagnosis of these two oral tumors was evaluated. The results showed no significant difference in mean microvessel count between the anti-CD105 (P = 0.803) and anti-CD34 (P = 0.279) antibody. The mean number of vessels was 18.75 and 59.72 for oral VMs immunostained with anti-CD105 and anti-CD34 antibody, respectively, whereas in OPG the mean number was 20.22 and 48.09, respectively. CD34 was found to be more effective than CD105 in identifying blood vessels. However, the anti-CD105 antibody seems to be more related to vascular neoformation. Overall, this study supports the role of angiogenic factors in the etiopathogenesis of oral VMs and PG, but the results showed that quantification of angiogenesis cannot be used as a marker for the differential diagnosis of these two types of lesions.