This was Giulio Romano's first work as an architect. The façade is divided vertically into five sections. The middle section presents a gabled entrance door, while the four side doors are surmounted by imposing wedge-shaped ashlar slates, giving a powerful upward thrust to the building.

The tension of the ashlar-work is tempered by the composed architectural layout of the piano nobile, and becomes a sheer rhythmic element in relation to the linear order of the second floor. In the courtyard, harmony of design is provided by flat ashlar-work at ground level and the slender two-storey trabeated loggia behind the front façade. Here again, Giulio Romano gave the language of the floors an abstract character.

Recent restoration work has revealed false windows in the vaulted ceiling of the Blue Room and original frescoes in the ground floor hall, where the grotesques and vine bower frescoed on the ceiling are dominated by the arms of the Stati family, the original owners of the building. The piano nobile is decorated with fine frescos by artists of Raphael's school. A smaller room houses the sequence, The Gods' Preferred Lovers, a traditional motif of the time, while a second room houses an uninterrupted frieze, divided into false frames, spaced out by putti and female caryatides, and showing episodes from the life of Julius Caesar.

Palazzo Cenci now houses the European Affairs Standing Committee, senators' offices and administrative services, in a spirit of conservation of the multifunctional tissue proper of the historic nature of the building.