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In this paper, an assessment of the natural radioactivity level, radon exhalation, metal contamination, and mineralogy of a granodiorite rock sample from Stilo, in the Calabria region, Southern Italy is presented as a case study. This rock was employed as a building material in the area under study. The specific activity of 226Ra, 232Th and 40K natural radioisotopes was assessed through high-purity germanium (HPGe) gamma-ray spectrometry. Then, several indices such as the absorbed gamma dose rate (D), the annual effective dose equivalent (AEDE), the activity concentration index (ACI) and the alpha index (Iα), were quantified to determine any potential radiological health risk related to radiation exposure from the analyzed rock. Furthermore, E-PERM electret ion chambers and inductively coupled plasma mass spectrometry (ICP-MS) measurements were carried out to properly quantify the radon exhalation rate and any possible metal pollution, respectively. In particular, to further address metal pollution factors, the geo-accumulation index (Igeo) was calculated to properly address the toxicity levels of the ecosystem originating from the detected metals. Finally, with the aim of successfully discriminating the provenance of such naturally occurring radionuclides, a combined approach involving X-ray diffraction (XRD) and µ-Raman spectroscopy was employed for the identification of the main radioisotope-bearing minerals characterizing the investigated granodiorite. The results achieved in this case study can be taken as the basis for further inquiries into background levels of radioactivity and chemical contamination in natural stone employed as building materials. [ABSTRACT FROM AUTHOR]