The bust of Isabel of Portugal (1503-1539) is represented in profile in a profusely sculpted frame, just like the relief carving of Emperor Carlos V (E291) that is paired with this one.

Beginning with the image of the Empress appearing on medals he, himself, had crafted at an earlier date, Leoni represents her with the same clothing and jewels. These are repeated in various of his works and constitute her most customary image.

The detailed and precise style of the bust is similar to that of a goldsmith, contrasting with the powerful reliefs of the architectural frame, which follows typically Renaissance motives. Outstanding are the caryatid and Atlantes that flank the bust. On the relief of Carlos V, those figures are turned to look at him, but here, they look straight ahead.