In order to test the value of an integrated approach for the analysis of health risks at contaminated sites, an integrated health risk assessment in a mining area was performed following 3 steps: 1) Environmental monitoring of surface soil, 2) assessment of exposure to metals in children and native rodents, and 3) DNA damage evaluation (comet assay) in children and rodents. These aspects also were studied in less exposed populations. Our results in humans showed that children living in the most polluted area (Villa de la Paz, Mexico) had higher lead blood concentrations (geometric mean of 13.8 μg/dL) and urinary arsenic levels (geometric mean of 52.1 μg/g creatinine) compared to children living in a control area (Matehuala, Mexico; blood lead of 7.3 μg/dL; urinary arsenic of 16.8 μg/g creatinine). Furthermore, the exposed children also had increased DNA damage (tail moment mean in Villa de la Paz of 4.8 vs 3.9 in Matehuala; p < 0.05). Results in rodents were identical. Animals captured in the polluted area had higher levels of arsenic (geometric mean of 1.3 μg/g in liver and 1.8 μg/g in kidney), lead (0.2 μg/g in liver and 0.9 μg/g in kidney), and cadmium (0.8 μg/g in liver and 2.2 μg/g in kidney), and increased DNA damage (tail moment mean of 18.2) when compared to control animals (arsenic in liver of 0.08 μg/g and kidney of 0.1 μg/g; lead in liver of 0.06 μg/g and kidney of 0.3 μg/g; cadmium in liver of 0.06 μg/g and kidney of 0.6 μg/g; and tail moment of 14.2). With the data in children and rodents, the weight-of-evidence for health risks (in this case DNA damage) associated with metal exposure in Villa de la Paz was strengthened. Therefore, a remediation program was easier to justify, and a feasibility study at this site is under way.