Background: Ramsar (Mazandran province) is known for its extremely high levels of natural background radiation. Although no excess cancer rate is reported in these areas by epidemiological studies, the study of tumor markers in the inhabitants of these areas may shed some light on the impact of high levels of background radiation on cancer induction. Materials and Methods: The level of background gamma radiation as well as indoor radon was determined using RDS-110 and CR-39 dosimeters. Thirty five individuals from a high background radiation area (HBRA) and 53 individuals from a normal background radiation area (NBRA) were randomly selected to participate in the study. Commercial ELISA kits (sandwich type ELISA tests) were used to measure the serum levels of PSA, CA15.3, CA125, Cyfra21-1, CEA, CA19.9, AFP and Tag72 tumor markers. Results: Among the eight biomarkers investigated, the means of PSA, CA15.3, CA125, CA19.9 and AFP concentrations between the HBRAs and NBRAs were not significantly different. However, Cyfra21, CEA and Tag72 in HBRA group revealed statistically significant increases compared to those of NBRA group (P<0.05). Furthermore, a statistically significant correlation between the external gamma dose as well as indoor radon level and the concentration of CEA (P<0.001), Cyfra-21(P<0.001) and TAG 72 (P<0.001 and 0.01 respectively) biomarkers were observed. Conclusion: Chronic exposure to high background radiation induces significant alterations in Cyfra21, CEA and Tag72 levels. We believe that studies with other relevant tumor markers might overcome the limitations of epidemiological studies on cancer incidence in high background radiation areas.