Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors. Its incidence is rated as one among the highest in the world and the use of tobacco in various forms is increasingly associated with the cause of OSCC. Levels of serum copper and iron was estimated and compared among subjects with tobacco habits and healthy controls. OSCC patients were categorized according the tobacco habits. Serum estimation of copper and iron was done using atomic absorption spectrophotometry and spectrophotometry. In this study, the level of copper was significantly higher in OSCC patients with smoking habit than in non smokers. Significantly low levels of iron were found in OSCC patients with smoking habits. The present study revealed a progressive increase in level of copper with decreasing iron concentration in serum of OSCC patients. The study hypothesizes that this imbalance may be one of the major factors responsible for the progression of oral cancer.