The outcome of different studies on the role of Zn & Mo in esophageal cancer (EC) is conflicting. Here, the levels of those elements in hair as well as food grain of two different ethnic populations across two continents have been studied to explore their role in EC. Two different ethnic populations are taken from (i) Eastern Cape, South Africa (RSA), an area of very high incidence of EC and (ii) West Bengal, India, an area of low incidence of that disease. Each ethnic population is divided into two groups: case and control (n=30 for all groups). Hair samples from all groups and food grain from RSA and India are analyzed for Zn & Mo content. This study shows a strong correlation between reduced levels of those elements in hair and the development of EC in RSA (both Zn &Mo: p < 0.0001), though it is only suggestive in Indian context (both Zn & Mo p ? 0.05). Interestingly, control group of RSA shows significantly reduced level of those elements in hair even with respect to Indian case group (Zn: p<0.001 & Mo: p< 0.00001). Food grain from RSA has significantly reduced level of those elements with respect to India (both Zn & Mo: p <0.0001). This deficiency of Zn & Mo in food grains can be correlated to the deficiency of those elements in hair of RSA population. The deficiency of Zn & Mo can be correlated to the development of EC.