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A tall public building in Naples (Italy) has recently undergone a seismic vulnerability assessment, following the new Italian code requirements. The building is about 100 m high and is founded on a piled raft floating in a thick layer of soft pyroclastic and alluvial soils. On the basis of a conventional subsoil classification, the inertial seismic actions on the building would lead to expensive measures for seismic retrofitting. By contrast, if site effects and soil-structure interaction are adequately addressed the picture is completely different. First, free-field seismic response analyses highlighted the beneficial effects of a peat layer, acting as a natural damper on the propagation of shear waves. Finiteelement analyses of pile-soil kinematic interaction were then carried out to define the foundation input motion, which was found not to be significantly affected. The effects of inertial interaction were evaluated accounting for soil-foundation compliance; they resulted in an increase of the structural period of vibration, while the overall damping did not change compared to that of the fixed-base structure. The increased structural period led to further reduction of spectral acceleration. The results could lead to significant impacts on the seismic assessment of slender buildings founded on piles embedded in deformable soils.