Myofibroblasts (MF) and angiogenesis are important factors in the development and expansion of cystic lesions, where these cells secrete growth factors and proteases, stimulating angiogenesis, matrix deposition and cell migration, affecting the growth of these periapicopathies. The present study aimed to evaluate the immunohistochemical expression of CD34 and ?-SMA in radicular cysts (RC) and residual radicular cysts (RRC), with the purpose of contributing to a better understanding of the expansion and progression of these periapical lesions. The present study os a descriptive, quantitative and comparative analysis of positive CD34 and ?-SMA immunohistochemical expressions in 30 RC and 30 RRC specimens. ?-SMA expression was evaluated in the fibrous capsule of the lesions, at 100x magnification below the epithelial lining. A total of 10 higher immunostaining fields were selected and subsequently, positive cells were quantified at 400x magnification, averaged per field. Regarding the angiogenic index, immuno-labeled microvessel counts for the anti-CD34 antibody were performed in 10 fields at 200x magnification. Statistically significant differences regarding ?-SMA immunostaining were observed (p = 0.035), as well as a correlation between ?-SMA versus CD34 (p = 0.004) in RRC. However, the angiogenic index obtained by immunostaining for CD34 indicated no statistical difference between lesions. Intense inflammatory infiltrates were predominant in RC, while mild and moderate degrees were more commonly observed in RRC (p <0.001). Intense inflammatory infiltrates were also more often noted in larger RRC (p = 0.041). Inflammatory infiltrates showed no significant correlation with ?-SMA and CD34 immunostaining. The results indicate that the significant correlation found between the presence of MF and the angiogenic index are related to the repair process in RRC.