We use new (micro-)structural, petrofabric, kinematic, and vorticity data to investigate the origin and deformation conditions of the opposite shear senses (i.e., top-to-the-SSE and -NNW shearing) recorded in the metamorphic rock pile of the Cycladic Massif on Ios Island, Greece. We focused our analyses on the contact between the Cycladic Blueschist Unit and the underlying Cycladic Basement as well as on the upper structural levels of the latter. The opposite shear senses are observed within the same foliation fabric, and they coexist at outcrop scale. Our observations showed that within foliation-parallel veins displaying top-to-the-SSE and top-to-the-NNW shear sense quartz is recrystallized in the grain boundary migration (GBM)/subgrain rotation (SGR) transition and SGR regimes, respectively. Integration of the observations from gneiss/schist samples showed that the SSE-directed shearing possibly commenced at the GBM/SGR transition and continued under SGR. In turn, top-to-the-NNW shearing occurred exclusively within SGR. We suggest that the opposite shear senses were operated asynchronously through foliation reuse under plane strain conditions. Early top-to-the-SSE shearing is associated with increasing simple shear component of deformation towards the contact between the two units, whereas subsequent reversal to top-to-the-NNW shearing is characterized by distributed general shear deformation throughout the study area. Foliation-parallel NNW-directed shearing progressively localized within ductile to brittle normal-sense zones that crosscut the foliation.