Fibroblasts represent the main cellular population in the connective tissue; they have a central role in extracellular matrix (ECM) synthesis, degradation and remodeling. These cells may express a substantial heterogeneity regarding their morphology and functions in pathological conditions and during tissue remodeling. Myofibroblasts are a good example for heterogeneity and phenotypical changes. These cells can be morphologically and immunologically defined by the expression of specific cytoskeleton proteins. Myofibroblasts show cytoplasmic actin microfilaments organized as stress fibers and interconnected by gap or adherens junctions. These cells come also in contact with extracellular matrix by focal contacts. Myofibroblasts play fundamental roles in pathologic conditions, even by activation and proliferation or by deletion. Moreover, these cells seem to be involved in formation and repair of the ECM compounds, proliferation and differentiation of the epithelial, vascular or neurogenic elements. The purpose of the present study is to emphasize the presence and distribution of myofibroblasts in the reactive stromal tissue of granulation tumors in the oral area, fibroinflammatory epulis and giant cells peripheral granuloma, by means of immunocytochemical and transmission electron microscopy studies. Both tumor types shown a common characteristic of the presence of reactive inflammatory stromal tissue and myofibroblasts are a common issue.