Deficiency of vitamin B12 and folate is associated with causation of certain precancerous conditions and cancer.The present study was carried out on 56 controls, 167 patients with oral precancerous conditions (OPC) and 214head and neck cancer patients, to evaluate the plasma vitamin B12 and folate levels to determine their associationwith tobacco habits and vegetarianism and several sociodemographic factors. The subjects were interviewed using ahealth habit and diet questionnaire at the time of blood collection. Simultaneous estimations of plasma vitamin B12and folate were done by Dual Count Radioassay. It was found that the habit of tobacco consumption, lower educationand low income were among the risk factors. A decrease in the plasma vitamin B12 and folate levels with respect totobacco habits, disease progression, and vegetarian diet was also observed. The individuals in the ower quartile forvitamin B12 and folate were at a higher risk of developing OPC, as compared to those in higher quartiles. Similarly,the patients with OPC in lower quartiles were found to be at a higher risk of developing cancer than their counterparts.There was a significant positive correlation between vitamin B12 and folate levels in the subjects consuming tobacco,and more so in patients with OPC (r=0.4330, p=0.000). Folate levels were significantly lower in patients with advancedas compared with early disease (ANOVA p=0.006 and Spearman’s Rho = -0.211 and p=0.01). The results suggest,potential significance of plasma vitamin B12 and folate levels in head and neck malignancies which needs to beconfirmed by further studies on a large population.