The compositional variability of the lithospheric mantle at extensional settings is largely caused by the reactive percolation of uprising melts in the thermal boundary layer and in lithospheric environments. The Alpine-Apennine (A-A) ophiolites are predominantly constituted by mantle peridotites and are widely thought to represent analogs of the oceanic lithosphere formed at ocean/continent transition and slow-to ultraslow-spreading settings. Structural and geochemical studies on the A-A mantle peridotites have revealed that they preserve significant compositional and isotopic heterogeneity at variable scale, reflecting a long-lived multi-stage melt migration, intrusion and melt-rock interaction history, occurred at different lithospheric depths during progressive uplift. The A-A mantle peridotites thus constitute a unique window on mantle dynamics and lithosphere-asthenosphere interactions in very slow spreading environments. In this work, we review field, microstructural and chemical-isotopic evidence on the major stages of melt percolation and melt-rock interaction recorded by the A-A peridotites and discuss their consequences in creating chemical-isotopic heterogeneities at variable scales and enhancing weakening and deformation of the extending mantle. Focus will be on three most important stages:(i) old (pre-Jurassic) pyroxenite emplacement, and the significant isotopic modification induced in the host mantle by pyroxenite-derived melts, (ii) melt-peridotite interactions during Jurassic mantle exhumation, i.e. the open-system reactive porous flow at spinel facies depths causing bulk depletion (origin of reactive harzburgites and dunites), and the shallower melt impregnation which originated plagioclase-rich pe-ridotites and an overall mantle refertilization. We infer that migrating melts largely originated as shallow, variably depleted, melt fractions, and acquired Si-rich composition by reactive dissolution of mantle pyroxenes during upward migration. Such melt-rock reaction processes share significant similarities with those documented in mod oceanic peridotites from slow- to ultraslow-spreading environments and track the progressive exhumation of large mantle sectors at shallow depths in oceanic settings where a thicker thermal boundary layer exists, as a consequence of slow-spreading rate.