Villa del Principe is the most extensive and sumptuous noble residence of the sixteenth century in Genoa. The construction works of the complex, which recovered and expanded a series of existing buildings in the area, began in 1521 at the behest of Andrea Doria, a skilled admiral and legendary man of arms. After an interruption, the construction of the Palace resumed in 1528, the year in which Andrea entered the service of Charles V, Emperor of the Holy Roman Empire and King of Spain. The first cycle of the Palace's works was completed in 1533, on the occasion of Charles V's visit to Italy, who was welcomed to Genoa with great pomp and was hosted in the admiral's residence.

Villa del Principe, overlooking the sea and characterized by a large courtyard bordered by terraced porticoes, follows the model of porticoed residences typical of the Hellenistic-Roman tradition and revived in the Renaissance period. Due to this characteristic, and more generally considering the entire complex, the palace represents a unique example in Genoese architecture of the period, suitable for the exceptional role and figure of Andrea Doria.

The artworks decorating Villa del Principe reveal the greatness of Admiral Andrea as a patron of the arts. He entrusted the decoration of his residence to Pietro Bonaccorsi, known as Perin del Vaga, an artist who had previously collaborated with Raphael in Rome, whose art was characterized by a cultured and refined language. The painter, a protagonist of the Roman scene in the years before the Sack of Rome in 1527, created in the Villa one of the most important Renaissance fresco cycles in northern Italy. In addition to frescoes and stuccoes, Perino designed tapestries, furnishings, and sculptures, choosing themes from ancient mythology and Roman history, through which he celebrated the figure of Doria, admiral, military leader, and de facto ruler of Genoa.