There is evidence that acute periapical lesions present a greater potential for cyst formation. Recently, it was found that these lesions have cells with characteristics of pluripotent stem cells, which may influence cyst development. However, a more complete phenotype investigation of stem cells in a specific sample of periapical abscesses is required. The aim of this study was to analyze the immunohistochemical expression of mesenchymal stem cell (MSC) markers in periapical abscesses and to evaluate differences in their expression in relation to acute and chronic periapical lesions.Immunohistochemistry was used to access MSC marker expression (CD44, CD73, and CD105) in samples of periapical abscesses (n = 10), granulomas (n = 10), cysts (n = 10), and apical papillae (n = 10). Immunohistochemical expression was evaluated by a quantitative scoring system. The chi-square test was used to assess the association between MSC marker expression and the histopathological diagnosis at a 5% significance level.CD44 and CD73 immunostaining was observed in mesenchymal cells located in the outer portion of the abscess and periapical cyst specimens. CD105 immunoexpression was found predominantly in mesenchymal and vascular endothelial cells of the lesions studied. MSC marker expression was higher in the periapical abscesses, with a significant association between MSCs and the histopathological diagnosis of an abscess (P < .05).The periapical region is a rich source of MSCs. The greater presence of MSCs in periapical abscesses found in this study could hold an important clue into understanding the pathological pathway of periapical cyst formation.