Background: Aberrant glycosylation is the universal feature of cancer and components of various glycoconjugates, such as sialic acid is found to rise in various malignancies. The objective of this study was to evaluate the serum and salivary sialic acid in oral potentially malignant disorders (OPMD) and oral cancer (OC) to investigate the possibility of using this as a diagnostic marker. Materials and Methods: The study included 85 subjects, who were grouped as control (30), OPMD patients (25), and oral cancer patients (30). Serum and unstimulated whole saliva was collected from subjects of all groups and sialic acid estimation was done using spectrophotometry. The results were tabulated and analyzed statistically. Results: The mean serum sialic acid levels in normal, OPMD, and oral cancer group were 7.515, 19.620, and 55.235 mg/dL, respectively, whereas the levels of salivary sialic acid were 1.5113, 2.3302, and 9.0304 mg/dL, respectively. A very highly significant rise (P < 0.005) in serum and salivary sialic acid was observed in the study subjects compared with that of the control. Conclusions: The present study showed a significant and gradual increase in serum and salivary sialic acid from control to oral potentially malignant disorders to oral cancer. From this study we can suggest that sialic acid can be used as a reliable biomarker. As this monosaccharide is observed in saliva in detectable quantity, saliva can be used as a diagnostic medium for screening and early detection of oral cancer.