Pyroxenite-peridotite sequences from the External Liguride (EL) Jurassic ophiolites (Northern Apennines, Italy) consist of portions of fertile MORB mantle that were modified by deep melt infiltration and melt-peridotite reaction. They represent an excellent natural example of a MORB-like veined mantle including unmodified peridotite, pyroxenite layers and metasomatized peridotite. We carried out a spatially controlled Hf isotope study on these mantle sequences to investigate how the Nd and Hf isotopic systems are affected by pyroxenite emplacement and melt-peridotite interactions. Present-day LuHf isotopic compositions of these lithologies show a large range of 176Lu/177Hf and 176Hf/177Hf ratios that are correlated with their Nd isotopic compositions. Pyroxenite-free peridotites delineate a HfNd isotope array that corresponds to a Proterozoic age (> 1.5 Ga) which is likely related to the accretion to the subcontinental lithosphere of this mantle sector. Heterogeneous 176Hf/177Hf isotopic compositions in pyroxenites mostly correlate with the significant variations of 176Lu/177Hf ratios and reflect variable garnet abundance in the primary modal assemblage. Over time, the pyroxenites acquired a large range of εHf values, which encompass the global range of HfNd isotopes in ocean ridge basalts. Infiltration of pyroxenite-derived melts led the host peridotite to acquire low Lu/Hf ratios with the consequent development of 176Hf/177Hf ratios lower than in the unmodified peridotite, generating an equivalent of an enriched mantle component. This melt-peridotite interaction likely occurred during the pyroxenite emplacement 430 Ma ago, as confirmed by two LuHf local pyroxenite-peridotite isochrons. The chemical and isotopic changes produced, over time, a spread of HfNd isotopic signatures of the EL veined mantle, covering almost the entire range of published MORB compositions. Pyroxenite emplacement and local metasomatism of the host peridotites thus created HfNd enriched mantle domains, making the EL veined mantle the first reported natural example of an enriched MORB-like mantle that formed through the combined effect of deep emplacement of pyroxenite and pyroxenite-peridotite interaction. The structure and isotopic characteristics of the EL veined mantle were used to model the isotopic compositions of melts produced by decompression melting of three-component heterogeneous mantle sources, providing an additional scenario to the generation of EMORB erupted at mid-ocean ridge settings. Our results emphasize the potential role of deep pyroxenite infiltration in modifying the host peridotites by interaction with pyroxenite-derived melts and creating heterogeneous mantle domains.