Introduction: Sialic acids are important terminal sugars of the carbohydrate chains of cell membrane glycoproteins and glycolipids. The progressive rise in total sialic acid (TSA) levels has been significantly associated with tumor progression and metastasis. Materials and Methods: Samples of 2 ml of unstimulated whole saliva were collected from 20 healthy patients, and 20 cases of histopathologically confirmed oral pre-cancer patients and 20 cases of histopathologically confirmed oral squamous cell carcinoma (OSCC) patients, using the method of Navazesh. Estimation of total sialic acid was done by the histochemical method of Yao et al. Results: The study revealed significantly elevated total sialic acid (TSA) levels in the saliva of oral precancer and OSCC patients, yielding a mean value of 59.75 ± 7.29 mg/dl and 204.85 ± 60.38 mg/dl, respectively, against the mean value of 21.65 ± 5.71 mg/dl of the healthy controls. Also, high total sialic acid (TSA) levels in the well-differentiated squamous cell carcinoma cases were appreciable to those of moderately differentiated ones. Discussion and Conclusion: The result suggests the correlation of elevated salivary TSA levels with the progression of OSCC. In conclusion, the study indicates that the glycoprotein metabolism is significantly altered in the saliva of patients, with both oral pre-cancer and OSCC. © 2017 Elsevier B.V., All rights reserved.