β2 -Microglobulin is the invariant chain of the Major Histocompatibility Class I (MHC-I) molecule on the cell surface of all nucleated cells and it reflects the cell turn over. Altered glycosylation of glycoconjugates is among the important molecular changes that accompany malignant transformation. The objectives of this study were to validate the diagnostic value of serum β2–microglobulin, Total Sialic Acid (TSA) and Lipid-Bound Sialic Acid (LSAB) and to correlate these parameters with the stages of the malignancy. Clinically and histopathologically proven 40 oral cancer patients were selected for the study. According to TNM stage of cancer, patients studied 11, 8, 10, 11 were of stages I, II, III and IV respectively. 40 healthy controls were selected for comparison. β2 -Microglobulin was estimated by ELISA and total sialic acid and lipid-bound sialic acid determined by the spectrophotometric method of Plucinsky et al. The concentration of β2-microglobulin, total sialic acid and lipid-bound sialic acid were significantly elevated in different stages of oral cancer patients when compared with the controls. Circulating levels of these biomarkers were also elevated significantly among different clinical stages with progressive rise from stage I to stage IV of the disease and found to reflect tumor burden. These biomarkers have good sensitivity, specificity and efficiency values for oral cancer. Thus, findings of the study suggest that the evaluation of these markers would be useful in assessing early malignant change, increasing accuracy of clinical diagnosis and also in assessing the spread and invasiveness of the cancer of the oral cavity.