Attic dusts were examined as historical archives of anthropogenic emissions, with the goal of elucidating the enrichment pathways associated with hydrothermal exploitation of Cu, Pb, and Zn minerals in the Bregalnica River basin in the eastern part of the Republic of Macedonia. Dust samples were collected from 84 settlements. Atomic emission spectrometry and mass spectrometry with inductively coupled plasma were applied as analytical techniques for the determination of 69 element contents. Multivariate analysis was applied for the extraction of dominant geochemical markers. The lithogenic distribution was simplified to six dominant geochemical markers: F1: Ga-Nb-Ta-Y-(La-Gd)-(Eu-Lu); F2: Be-Cr-Li-Mg-Ni; F3: Ag-Bi-Cd-Cu-In-Mn-Pb-Sb-Te-W-Zn; F4: Ba-Cs-Hf-Pd-Rb-Sr-Tl-Zr; F5: As-Co-Ge-V; and F6: К-Na-Sc-Ti. The anthropogenic effects on the air pollution were marked by a dominance of F3 and secondary dominance of F5. The fifth factor also was determined as a lithogenic marker for the occurrence of the very old Rifeous shales. The first factor also presents a very unique association that despite the heterogeneity relays on natural phenomena of tracking the deposition in areas of Proterosoic gneisses; related to the distribution of fine particles was associated with carbonate-silicate volcanic rocks. Intensive poly-metallic dust depositions were recorded only in the surroundings of localities where the hydrothermal extractions are implemented. Long-term deposition can be considered as pollution indexes for these hot spots. This mainly affects the Cd, Pb, and Zn deposition that is as high as 25, 3900, and 3200 mg/kg, respectively.