Background: Among all oral malignancies, the most common malignancy contributing to about 90% is oral squamous cell carcinoma (OSCC). The alterations in the circulatory cholesterol levels have been found to be associated with head and neck cancers. Present study was aimed to evaluate alterations in plasma lipid profile in oral cancer patients and its association with histological grading. Material and Methods: Present study was s prospective cross sectional study, conducted in patients with malignancy, lesions diagnosed on the basis of histopathological examination were considered as cases. Age & gender matched, healthy volunteers were taken as control. Results: In present study, 40 cases & 40 controls were studied. Majority of cases were from 41-50 years (35 %) & 31-40 years (32.5 %), were male (87.5 %), had history of alcohol consumption (67.5 %) & had history of tobacco consumption (67.5 %). In present study, majority had primary site of involvement as tongue (37.5 %) & buccal mucosa (22.5%), majority were stage III (47.5 %) & stage I (20 %), as per histopathological grading as well differentiated (57.5 %) & moderately differentiated (35 %). We compared various lipid levels (Cholesterol, TG, HDL, LDL & VLDL) among cases & controls. Levels of Cholesterol, TG, HDL & LDL were lowest in patients with oral malignancies as compared to healthy controls & difference was statistically significant (P<0.05). In present study, various lipid levels (Cholesterol, TG, HDL, LDL & VLDL) among various histopathological grading (well differentiated, moderately differentiated & poorly differentiated) oral malignancies were comparable & difference was statistically not significant (p>0.05). Conclusion: The lower levels of plasma cholesterol and other lipid constituents in patients might be due to their increased utilization by neoplastic cells for new membrane biogenesis.