The objective of the study was to investigate the possible role of manganese and copper (Mn/Cu) imbalance of the food chain in the focally increased occurrence of Creutzfeldt-Jakob disease (CJD). Mn and Cu concentrations in soil, drinking water and foodstuffs collected from households in the region of focal accumulation of CJD patients and the control region were measured by FAAS. Considerably higher Mn/Cu ratios in the studied region than those in the control region were found for soil (49.3 vs. 21.1), honey (8.05 vs. 4.86), and for the main local food items: potatoes (2.09 vs. 1.07) and bread (5.85 vs. 5.35), however, only soil and potatoes were of statistical significance. The results could indicate a rare coincidence of the verified endogenous CJD risk (genetic) with a very probable exogenous CJD risk factor (Mn/Cu dietary/environmental imbalance), but whether and how this coincidence may contribute to the unique, continual temporo-spatial clustering of genetic CJD should be investigated in further studies.