Rodingites, a high-Ca content variety of metasomatic rocks, have been found in the Veria-Naousa and Edessa ophiolites, in northern Greece. The rodingites from both areas are characterized by a substantial overprint of primary textures. Coupled field and petrographic observations reveal derivation from ultramafic and mafic protoliths. The mineral phases in the ultramafic-derived rodingites (UDR) include mainly diopside, garnet, chlorite, tremolite, and Fe[sbnd]Ti oxides whereas mafic-derived rodingites (MDR) contain diopside, garnet, vesuvianite, chlorite and quartz. Here we present, for the first time, whole rock Cu, Zn and Fe isotopic data for the UDR and MDR from the Veria-Naousa and Edessa ophiolites, to investigate the evolution of this peculiar metasomatic lithotype. All the studied rodingites present δ65Cu values varying from −0.17 ± 0.03‰ to +0.62 ± 0.05‰ and δ66Zn ranging from −0.06 ± 0.03‰ to +0.74 ± 0.06‰. 0.0. Copper isotope ratios are systematically heavier in rodingites compared to their respective protoliths whereas Zn shows a diverse behavior with enrichment in its light isotopes (group 1: comprising all the UDR and a MDR sample) or in its heavy isotopes (group 2, the rest MDR samples). The same gabbroic protolith can lead to both group 1 and 2 rodingites with respect to their Zn isotopic ratios. Alkaline conditions of the hydrothermal metasomatic fluids and the inferred sulfide and bisulfide ligands promoted mobility of Cu and Zn and have likely played a major role to their isotopic behavior in the rodingites. In contrast, Fe isotopes have not fractionated during rodingitization. Complex metasomatic processes, such as rodingitization, have a clear impact on stable isotope fractionation, which is decoupled between the Cu, Zn and Fe isotope systems. The lack of correlation between isotope ratios and any mineralogical or elemental indicator highlights the absence of any profound relationship between isotope fractionation and mineral phases, which could reflect the stage and evolution of rodingitization. The consistent isotopic behavior of Cu indicates a promising geochemical tool to distinguish metasomatized and non-metasomatized samples within different observed groups, and define conditions and parameters during Ca-metasomatism, regardless the degree of rodingitization, prior alteration and various protoliths compositions. Additionally, Zn isotopes give a useful insight on the metasomatic conditions for both ultramafic and mafic precursors defining local pH changes coupled with available ligands, HS−, where Cu isotopes alone would not be able to describe.