BackgroundOral submucous fibrosis (OSMF) is a prevalent precancerous condition of the oral cavity and an ambiguity to clinicians because of its indistinguishable etiopathogenesis. Previous studies could not establish a definite role of mast cells (MCs) in the fibrosis of stroma. The present study was done to study the histopathological changes in OSMF and to determine the association of mast cells (MCs) and their degranulated components with vascularity.MethodsA retrospective case-control study involved 40 cases of various histopathological grades of OSMF and was compared with 10 cases of normal buccal mucosa by using a cluster of differentiation 117(CD117) kit for the identification of MCs and Masson’s trichrome stain to study the number of blood vessels (BVs).ResultsThe present study indicated that advanced cases of OSMF had keratinized epithelium with atrophic changes and moderate to advanced fibrosis of stroma with the involvement of underlying muscles. The MC density and the number of blood vessels were progressively reduced in OSMF as the grade advanced compared to healthy controls.ConclusionAn increase in the mast cell density in the initial stages of OSMF suggests their definite role in the initiation of fibrosis and secondary changes to the epithelium such as atrophy.