Oral submucous fibrosis (OSF) is a potential precancerous condition of the oral cavity and oropharynx. The etiopathogenesis of this complex precancerous condition is still obscure. In addition to deleterious oral habits, malnutrition, and possible genetic predisposition, altered bioelemental status is also likely to play an important role in its pathogenesis. The present study analyzed 68 elements by inductively coupled plasma-mass spectroscopy in oral mucosa of normal and OSF individuals and some interesting alterations in elemental profile in the diseased tissue have been noted, indicating a homeostatic imbalance. These bioelemental alterations leading to homeostatic imbalance might be considered as an important biological event in the pathogenesis of OSF.