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This paper reports the first results of a study of 11 isotope systems (He/He, Ar/Ar, S/S, Cu/Cu, Ni/Ni, Sr/Sr, Nd/Nd, Pb/Pb, Hf-Nd, U-Pb, and Re-Os) in the rocks and ores of the Cu-Ni-PGE deposits of the Norilsk ore district. Almost all the results were obtained at the Center of Isotopic Research of the Karpinskii All-Russia Research Institute of Geology. The use of a number of independent genetic isotopic signatures and comprehensive isotopic knowledge provided a methodic basis for the interpretation of approximately 5000 isotopic analyses of various elements. The presence of materials from two sources, crust and mantle, was detected in the composition of the rocks and ores. The contribution of the crustal source is especially significant in the paleofluids (gas-liquid microinclusions) of the ore-forming medium. Crustal solutions were probably a transport medium during ore formation. Air argon is dominant in the ores, which indicates a connection between the paleofluids and the atmosphere. This suggests intense groundwater circulation during the crystallization of ore minerals. The age of the rocks and ores of the Norilsk deposits was determined. The stage of orebody formation is restricted to a narrow age interval of 250 ± 10 Ma. An isotopic criterion was proposed for the ore-bearing potential of mafic intrusions in the Norilsk-Taimyr region. It includes several interrelated isotopic ratios of various elements: He, Ar, S, and others. [ABSTRACT FROM AUTHOR]