Introduction: Odontogenic lesions are relatively common lesions and account for a substantial part of total oral biopsies by an oral pathologist. Some lesions like the keratocysticodontogenic tumor (KCOT) exhibit a locally aggressive behavior.Myofibroblasts (MFs) are specialized fibroblasts. These cells play a role in physiological processes like wound healing and pathologic conditions like reactive lesions, benign tumors, locally aggressive tumors and malignancies affecting oral cavity. Earlier, it was believed that the presence of Myofibroblasts (MFs) at the invasive front of the tumor was a part of the host defence mechanism against the tumor, but recent studies suggest that the presence of these cells at the tumor front promotes the growth and invasion of the tumor. The presence of Myofibroblasts has been reported in the stroma of many odontogenic lesions, including both cysts and tumors. Studies conducted both on odontogenic cysts and tumors revealed that the cells were particularly more in lesions with locally aggressive behavior like odontogenic keratocyst (OKC). The aim of the study was to evaluate the role of Myofibroblasts in KeratocysticOdontogenic Tumor and its objectives were to compare the expression and distribution pattern of Myofibroblasts in KeratocysticOdontogenic Tumor (KCOT) as compared to their expression in Oral Squamous Cell Carcinoma and to derive a co-relation between the stromal Myofibroblasts and the known biologic behavior of KeratocysticOdontogenic Tumor (KCOT). Material and Methods: The study specimen comprised of 30 Specimens of Keratocysticodontogenictumor(KCOT and10 Specimens of Oral Squamous Cell Carcinoma. Results: 7 out of 30 (23.30%) of the slides of keratocysticodontogenic tumor showed intensely positive staining to α-sma and 16 out of 30 (53.30%) of the slides of keratocysticodontogenic tumor showed moderately positive staining to α-sma. 8 out of 10 (80.00%) of the slides of oral squamous cell carcinoma showed intensely positive staining toα-sma and 2 out of 10 (20.00%) of the slides of oral squamous cell carcinoma showed moderately positive staining to α-sma. Conclusion: According to the results of our study, quantitative evaluation and pattern of MFs in KCOT which is accepted as aggressive odontogenic lesion shows positive results, but at the same time differs from that of OSCC. This suggests that there is a positive association of MFs and aggressiveness of the lesion at the growth front. To conclude, we feel that at this point of time, we can safely suggest that increase in number of Myofibroblasts and change in their distribution pattern are of great value in predicting the possible biologic behavior of such lesions, and may hold prognostic significance in the near future.