BACKGROUND: Cholesterol at either higher/lower level can be troublesome. Health issues related to higher than normal levels have received much public attention because of their relationship to incidence of heart disease, whereas implications of decreased cholesterol levels remain unclear. Present study tried to evaluate and correlate the decreased cholesterol levels in Oral cancer, Oral precancer and in tobacco abuse. METHODS: Total Cholesterol (TC), High Density Lipoproteins (HDL), Very Low Density Lipoproteins (VLDL), Low Density Lipoproteins (LDL) and Triglyceride (Tri) were estimated in 210 subjects. Out of these 210 subjects, 70 subjects were histopathologically confirmed Oral Cancer, 70 subjects were histopathologically confirmed Oral precancer (OPC) and 70, age and sex matched, healthy subjects who are not having Oral Cancer, Oral precancer and who had no history of any major illness in the past. These groups were subdivided into: Subjects with No Habit of Tobacco (NHT) and Subjects With Habit of Tobacco (WHT). RESULTS: There was significant decrease in TC, HDL, VLDL, and triglyceride in Oral Cancer group; and significant decrease in TC, and HDL in Oral precancer group as compared to Control. Mean serum lipid profile levels were not significantly different in subjects between NHT and WHT. CONCLUSIONS: There is an inverse relationship between serum lipid profile and Oral Cancer and Oral precancer. There was no overall significant correlation of serum lipid profile with tobacco abuse. J Oral Pathol Med (2010) 39: 141-148