Tobacco smoke may be one of the most common sources of cadmium (Cd) in the general population, particularly in the rising population of smokers in developing countries. Although a relationship between both cigarette smoking and environmental Cd contamination with prostate cancer exist, the mechanisms are unclear. Most prospective cohort studies found a positive association between current smoking and a fatal cancer of the prostate. We investigated the interaction between zinc and cadmium and the potential risk of prostate cancer in smokers. Serum cadmium level was significantly (P < 0.001) higher in smokers compared with non-smokers, the level in smokers was three-fold that in non-smokers. In contrast zinc was significantly (P < 0.001) reduced in smokers compared with non-smokers. Unlike Zn, Cu was significantly (P < 0.05) higher in smokers than in non-smokers. Iron (Fe) though higher in smokers was not significantly different. Zinc: cadmium ratio was very significantly (P < 0.001) reduced, implying high cadmium: zinc ratio. This ratio was 4.5-fold the level in non-smokers. Total protein, albumin and total globulin levels were all significantly (P < 0.001) reduced in smokers compared with non-smokers respectively. Potassium (K+) was significantly (P < 0.05) higher in smokers than in non-smokers. Magnesium (Mg) was significantly (p < 0.01) reduced in smokers compared to non-smokers. Altered Zn status culminating in high Cd:Zn ratio appears the central factor in smokers; leading to oxidative stress, DNA damage, mutation, impaired DNA repair, P53 expression, angiogenic effect of Cu and impaired vitamin A metabolism. These converge in the risk of the carcinogenic process, suggesting high Cd: Zn ratio as the critical determinant of the risk of prostate cancer in smokers and possibly a biomarker of susceptibility to this environmental disease.