Myofibroblasts are modified fibroblasts with smooth muscle like features characterized by the presence of contractile apparatus. Myofibroblasts have an important position in the inflammatory response. They produce matrix molecules such as collagen, glycosamino-glycans, tenascin and fibronectin in the interstitial space or basement membrane and play important role in growth, differentiation and wound healing which if deranged or separated can result in tissue fibrosis. Myofibroblasts interact with epithelial cells and other connective tissue cells and may thus control such phenomena as tumour invasion and angiogenesis. Myofibroblasts also promote invasion by altering the composition of the tumour micro environment and are prognostic. Myofibroblasts in the stroma of OSCC may influence proliferation and invasion, resulting in more aggressive tumour. Myofibroblasts in the stroma of odontogenic lesions also play an important role in their aggressive biological behaviour. As they are present in virtually every tissue, it is possible that they may play a role in multisystem diseases. Understanding the role of the stromal cells and extracellular matrix will allow us to identify more precise prognostic markers and potentially device new therapeutic options and prevent various diseases caused by these miraculous multipotential cells.