Lipids are the major cell membrane components, essential for various biological functions including cell growth and division for the maintenance of cell integrity of normal and malignant tissues. The changes in lipid profile have been associated since long with cancer and hypocholesterolemia has been observed in patients with cancers of various organs. The objective of the present study is to evaluate the alterations and clinical significance of plasma lipid profiles in untreated head and neck malignancies. The present case-control study comprises of newly diagnosed and histologically confirmed, 100 head and neck malignancy cases diagnosed between 1st July 2013 and 30th June 2014 in the Department of Otorhinolaryngology and Head and Neck Surgery, Gandhi Medical College, Bhopal. Fasting blood samples were collected and the lipid profile studied. In present study, the authors found that there is a preponderance of head and neck malignancy in the age group of 41-60 years, males having the higher incidence. Malignancy involving oral cavity were the commonest and majority were well differentiated. Statistically, there was a highly significant reduction of mean serum total cholesterol (TC), triglycerides and high density lipoproteins (HDL) in the subjects of head and neck malignancy as compared to the control group. TC and HDL were also found significantly lower among those with habit of tobacco consumption.