The impact of lithological heterogeneities on deformation, fluid flow and ore deposition is discussed based on the example of the Lavrion low-angle detachment partly accommodating gravitational collapse of the Hellenides orogenic belt in Greece. The Lavrion peninsula is characterised by a multiphase Pb-Zn-Fe-Cu-Ag ore system with a probable pre-concentration before subduction followed by progressive remobilisation and deposition coeval with the development of a low-angle ductile to brittle shear zone. The mylonitic marble below the detachment shear zone is composed of white layers of pure marble alternating with blue layers containing impurities (SiO2, Al2O3, carbonaceous material). Ductile mylonitic deformation is more pervasive in the less competent impure blue marble. We propose that localised deformation in the impure marble is associated with fluid circulation and dolomitisation, which in turn causes an increase in competence of these layers. Mineralised cataclastic zones, crosscutting the mylonitic fabric, are preferentially localised in the more competent dolomitic layers. Oxygen and carbon isotopic signatures of marble invaded by carbonate replacement deposits during ductile to ductile-brittle deformation are consistent with decarbonation coeval with the invasion of magmatic fluids. Mineralised cataclastic zones reflecting brittle deformation evolve from low 13C to low 18O signatures, interpreted as local interaction with carbonaceous material that trends toward the contribution of a surface-derived fluid. These features indicate that the Lavrion area records a complex deposition history influenced by the evolution of fluid reservoirs induced by the thermal and mechanical evolution of the marble nappe stack. Ore remobilisation and deposition associated with the activity of the low-angle detachment is (i) firstly related to the intrusion of the Plaka granodiorite leading to porphyry-type and carbonate replacement mineralisation during ductile-brittle deformation and (ii) then marked by progressive penetration of surface-derived fluids guided by strain localisation in the more competent levels leading to epithermal mineralisation associated with brittle deformation.