The paper deals with the seismic retrofit of an existing monumental building through a hybrid solution, applying an isolation system to a structure previously strengthened and stiffened. The case study was built in Rome in the middle of 1960s. Having a plan extension of about 2000m², with an inner decentralized open court, the building is a mixed steel-concrete structure. At the first level, it is characterized by R.C. pillars and two shear walls not symmetrically placed in plan. Upon it, there are two other levels made of steel frames. The first floor level is a "floating plane": consisting of a grid of steel beams, it bears loads transferred form the upper components. Through it, a structural continuity is ensured between portions having different stiffness, i.e. a wide upper steel part more deformable than the small lower R.C: lower. Resulting from a gravity-load design approach, without taking into account seismic actions, this monumental building is highly irregular at each level; with a noticeable asymmetry due to the shear walls distribution. These R.C. elements are the only ones having a certain horizontal stiffness at the upper levels, where the existing slender steel bracings are not placed in correspondence to the lower pillars. In this case, a hybrid solution for seismic retrofitting has been proposed. Considering the high deformability of the steel elements, not bearing seismic forces, the preventive strengthening actions refer mainly to R.C. components, including: the strengthening of the existing shear walls and the introduction of other two ones; the structural consolidation of the SAP-type slabs. In addition, the strengthening of the existing slender steel bracings is expected. Working on such stiffened structure, the isolation system introduces anti-seismic devices below the floating plane, using 32 HDRBs (f 600) and 8 sliders. This solution leads to increase the fundamental vibration period from T_FB= 0,563 s, valued for the fixed base, to T_ISO= 3,05 s, for the strengthened isolated solution, reducing the seismic action of 76%.