The heart of the collection, and the first of the interventions carried out in the palace by Giorgio Franchetti, was the so-called Cappella del Mantegna, with the image of San Sebastian in the center around which the baron conceived a striking architectural space, entirely covered with marble. Inspired by Venetian models (especially the church of Santa Maria dei Miracoli), the room reproduces the atmosphere of a Renaissance chapel, ideally set inside a patrician residence. Above a real altar is the canvas, one of Mantegna's most dramatic inventions. The work, purchased in 1893, still constitutes the icon of the museum today, maintaining the arrangement desired by the owner unchanged within a museum itinerary that has undergone inevitable changes and revisions over the years. The late result of a study on the theme of martyrdom that Andrea Mantegna had already undertaken in the canvases today at the Kunsthistorisches Museum in Vienna and in the Louvre, the Ca 'd'Oro painting deals with the representation of the Christian hero in new and somewhat disconcerting terms. , of tragic individual isolation. The saint, pierced by sixteen arrows, which envelop him in a sort of thorny three-dimensional cage, stands sadly in the center of a narrow niche, framed by a faux marble frame. Below, on the right, a scroll wrapped around the emblematic image of the extinguished candle that still lets a thin wisp of smoke breathe, bears the inscription Nihil nisi divinum stable est coetera fumus (nothing, except the divine, is stable, everything the rest is smoke), to underline the fragility of human nature.

Little is known of the original location of the Double Portrait, the first example of this type of portrait in Italian sculpture of the fifteenth century. The origin is undoubtedly to be found in classical art. In fact, even Mantegna in the fresco with San Cristoforo in the church of the Eremitani in Padua reproduces double portraits taken from Roman funerary steles. But here the author manages to create something completely new: a work steeped in ancient spirit but absolutely modern, with no real precedent in antiquity itself, a perfect balance between the realistic definition and the idealization of the individual. The characters depicted, perhaps real portraits, perhaps allegorical figures, are filmed when they are talking or singing, with their lips parted and their eyes turned in different directions. The hair, the modeling of the faces, the decorated dress of the female figure, the flower between the breasts, every detail is exquisitely rested, with extreme refinement and delicacy. Under the male figure the signature of the author in the Roman capital is clearly visible, as if to suggest that the original destination was a raised position, to allow easy reading.

In the lunette in Carrara marble, the Madonna and Child are caught in a very sweet affectionate attitude, under an arch decorated with two winged angels. Originally the work was located in the Church of the Zitelle on Giudecca where it was part of the decoration of the main altar. In the central figures of the relief, the cultured and updated personality of the Florentine sculptor is expressed in a scene of touching intimacy that sees the Mother depicted in the act of supporting the child, supporting his back with her right hand, to return the kiss that the Child gives her. offers with great naturalness. In the very human and intimate impetus that unites the two protagonists, the virgin's left hand pushes the closed book away from itself, as if wanting to remove the already established fate from the son. The classic pose of the two angels above, languidly leaning on the cornice, underlines the vitality of the scene below. the refined management of the drapery, the monumental layout and the calibrated balance of the composition, as well as the soft rendering of the anatomies, betray a direct knowledge of Michelangelo's art, approached by the artist in his Roman stays prior to his transfer to Venice in 1527.

The Crucifixion by Jan Van Eyck, one of the most important paintings in the collection that previously belonged to Baron Giorgio Franchetti. The small panel made in the Van Eyck workshop, under the supervision of the Master, was probably taken from one of the great artist's original drawings. The full autography of the work is still the subject of discussion and studies today. The small dimensions extraordinarily enhance the miniaturistic talent of the Flemish painter and his close collaborators. The Crucifix is perfectly central to the scene. Below, the Mother and St. John the Evangelist presented in deep sorrow, but composed, and not pervaded by despair like the group of women behind the Virgin. In the background, the idealized city of Jerusalem is represented down to the smallest detail. On the right is a group of knights who, indifferent, are leaving the place of execution to return to the city walls. Van Eyck's 'Ideal Jerusalem' bears a striking resemblance to Sana'a, the capital of Yemen. Incredibly, Sana’a is also surrounded by walls with the same typical tower-houses, and is divided into three districts (Arab, Turkish and Jewish). It cannot be excluded that the Flemish master was inspired by designs of the Yemeni city coming along the trade routes to and from the East.