Background: Immunohistochemical phenotype, distribution and significance of proliferation of myofibroblasts (a SMA positive cells) with evaluation of ultrastructure, in dentigerous cyst, odontogenic keratocyst and ameloblastoma were analyzed. Methods: The study included paraffin embedded blocks of ameloblastoma (n=22), odontogenic keratocyst (n=20), and dentigerous cyst (n=18). The expression of a SMA was determined by immunohistochemically stained section. The percentage of positive cells was calculated from a minimum of 1000 cells and H-score was expressed (% positive cells x intensity of staining). For transmission electron microscopy, fresh specimens were obtained from three patients and were fixed in 2.5% glutaraldehyde. The presence of cells with the ultrastructural characteristics of the myofibroblast was recorded. Results: The mean number of positive cells in the three groups was significantly different. The difference between odontogenic keratocyst and dentigerous cyst and also the difference between dentigerous cyst and ameloblastoma were not statistically significant. The mean number of positive cells in the odontogenic keratocyst was significantly higher than that in ameloblastoma. In ultra-structural evaluation, myofibroblasts exhibited abundant cytoplasmic microfilaments, basal lamina-like material, subsurface caveolae, pinocytic vesicles, rough endoplasmic reticulum, and mitochondries. Conclusions: The high frequency of stromal myofibroblast in the odontogenic keratocyst implies that myofibroblast can contribute to aggressive nature of this cyst, but between odontogenic cysts and ameloblastoma, the presence of stromal myofibroblast has no correlation with invasiveness.