The influence of extreme environments of volcanic origin over vertebrates and the cellular responses that these may give are almost unknown. The main objectives were to evaluate the exposure of mice to metals in the interior of houses of a small village settled inside a volcanic crater (Furnas, Azores), and the levels of apoptosis and metallothionein in the organs (lung, liver, and kidney) of those animals. Adult mice (Mus musculus) were captured in two areas, one with volcanic activity and the other without it over the last three centuries. In the excised organs, analysis of metals (Al, Cd, Pb, Zn), TUNEL assay for apoptosis, and immunohistochemistry for metallothionein were undertook. Mice from the area with volcanic activity presented higher levels of apoptosis and metallothionein than those from the area without volcanic activity. Such results were in agreement with the differences in metal burdens of the three organs, and interestingly these concentrations were similar to or higher than others found in heavily polluted areas outside the Azores. Thus, there may be a high risk of harmful effects for organisms, including humans, inhabiting areas with volcanism, where hazardous gases and metals in the air are very common during the entire day or even all year round.