Introduction:Oral submucous fibrosis (OSMF), a precancerous condition, is highly prevalent in the Indian subcontinent. Among many trace elements, copper and iron are required for the functioning of numerous enzymes. The biochemical alterations of these trace elements in the serum of patients with premalignant conditions can help in determining the staging of the disease, its appropriate treatment and as an indicator for prognosis.Aims and Objectives:The objective of the study was to evaluate the role of iron and copper as well as to identify the better predictor of the two in the diagnosis and progression of OSMF.Materials and Methods:The study sample consisted of 150 patients, out of which the cases group consisting of 100 OSMF patients and control group consisting of 50 individuals. All the cases were confirmed of having OSMF by histopathological examination. The blood sample was obtained from all 150 patients and evaluated by digital autoanalyzer photometer for serum level of copper and iron by the colorimetric method. The results obtained for cases and controls were compared by statistical analysis.Results:The mean serum copper level increases while the mean serum iron level decreases with the advancement in the severity of clinical and histological stages of OSMF.Conclusion:Biopsy is the gold standard to diagnose OSMF, but it is an invasive and time-consuming technique. However, nowadays, many recent advances are used to diagnose OSMF at an early stage and reduce its progression into late and reversible stages. The trace elements serve as potential prognostic and diagnostic markers for OSMF patients.