The Museo di Palazzo Grimani was originally the residence of Antonio Grimani (doge from 1521 to 1523), the current building is the result of architectural interventions carried out between 1532 and 1569 commissioned by the heirs, Vittore, procurator of San Marco, and Giovanni, patriarch of Aquileia.

Above all, the latter directly intervened in the design, perhaps using suggestions from Sanmicheli (to whom the entire structure was previously attributed), but above all referring to the treatise by Sebastiano Serlio. The result is a remarkable and admirable architecture that blends elements of Venetian and Tuscan-Roman tradition: particularly striking is, among others, the evocative atmosphere of the hall with the pyramidal skylight. The fusion of different artistic cultures is also evident in the wonderful pictorial decorations of the staircase and the rooms on the first floor, where painters such as Federico Zuccari, Francesco Salviati, Giovanni da Udine, Lambert Sustris, and Camillo Mantovano worked.

The palace housed the art and archaeology collections of Cardinal Domenico Grimani and of Giovanni, patriarch of Aquileia, who were also donors of substantial parts of their collections to the Republic, which formed the basis of the birth of the public Statuary of the Serenissima. The historical-artistic aspect of the monument only reflects the taste and cultural policy of the Grimani family, which built its fortune - social, economic, political - precisely between the two fundamental centers of Venice and Rome.

This makes Palazzo Grimani a unique piece in the Venetian context, comparable in cultural importance, while distinguishing between private and public commissions, to the works of Jacopo Sansovino in the area of Piazza San Marco, for the realization of which, moreover, the contribution of this family was fundamental.