Epidemiologic studies suggest that zinc (Zn) deficiency and high accumulation of cadmium (Cd) may be associated with increased risk of cancer. The incidence of mouth cancer has increased among females, who possess habits of chewing tobacco with gradients (areca nut and betel quid) and smoking tobacco in Pakistan. In present study, we measured the concentration of Cd and Zn in 96 mouth cancer patients (MCPs) and 110 female controls/referents (67 smoker and chewing tobacco), while 43 have none of smoking and chewing tobacco habits, belongs to different cities of Pakistan. Both controls and patients have same age group (ranged 35-65 years), socio-economic status, localities and dietary habits. The Zn and Cd were determined by flame/graphite furnace atomic absorption spectrophotometer, prior to microwave assisted acid digestion method. The Cd/Zn ratio in both biological samples was also calculated. The results of this study showed that the mean value of Zn was lower, while the mean concentration of Cd was higher in the blood and scalp hair samples of MCPs as compared to control subjects (p < 0.001). The controls chewing and smoking tobacco have high level of Cd in both biological samples as compared to those have not smoking or chewing tobacco (p < 0.012). The Cd/Zn ratio was higher in MCPs than control subjects. This study is compelling evidence in support of positive associations between cadmium, cigarette smoking, deficiency of Zn and cancer risk. (C) 2009 Elsevier B.V. All rights reserved.