In Assassin's Creed Brotherhood, Rome is the Italian city controlled by Ezio for most of the game.
Brotherhood continues Ezio Auditore's story after Assassin's Creed II. The main campaign is set primarily in Rome, where the Borgia family dominates politics and the Papal States. Ezio works to weaken Borgia influence, restore districts, recruit and train Assassins, and rebuild the local Brotherhood.
Rome functions as the game's main open world rather than merely serving as a short story location. Ezio can liberate areas, renovate shops and landmarks, and use recruited Assassins during missions. The city includes famous sites such as the Colosseum, the Pantheon, and the Castel Sant'Angelo, though the game represents them within a fictionalized historical narrative.
Florence and Venice are strongly associated with Ezio because they are major locations in Assassin's Creed II. Naples is also connected to the wider Italian setting and later series history, but it is not Brotherhood's principal city. The title's focus on Brotherhood management and Rome distinguishes it from the more geographically varied second game.