Statement of the Problem: Ameloblastoma is the most common odontogenic tumor which is slow-growing, locally invasive and exhibit specific biologic behavior and high recurrence rate. Likewise, odontogenic keratocyst is a developmental odontogenic cyst that has a high recurrence rate and aggressive behavior. There are limited studies considering the relationship between the angiogenesis factors and the biologic behavior of these lesions.Purpose: the aim of this study was to evaluate the mean density of vessels in odontogenic keratocysts and ameloblastoma and investigate its possible relationship with biological behavior of these lesions.Materials and Method: In this descriptive-analytic cross-sectional study, 40 cases, comprising 10 odontogenic keratocysts and 30 ameloblastomas (10 plexiform, 10 follicular, and 10 unicystic type) were selected and were stained immuno-histochemically with CD34 and CD105. The micro vessel density was assessed and compared in all groups. T- test for the independent samples’ One- way Anova, Wilcoxon test and Tukey tests were adopted for statistical analysis.Results: A statistically significant difference was observed in mean vascular density (MVD) between the odontogenic keratocyst and ameloblastoma groups concerning the CD105 and CD34 markers (p= 0.005, p= 0.000, respectively). The MVD was significantly higher in ameloblastomas than odontogenic keratocyst. MVD with CD34 was significantly higher than MVD with CD105 in ameloblastomas (p= 0.00).Conclusion: It can be suggested that angiogenesis might be one of the mechanisms that is more possible to contribute the aggressive biological behaviors in ameloblastoma rather than odontogenic keratocyst.