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The Centro District was one of the four districts of Rome, being characterized by its large cityscape and tall buildings. During the Renaissance, the Centro district, like the Antico and Campagna districts, fell into disrepair under the House of Borgia, as its influence led to the majority of the shops being closed down.
Five Borgia Towers ruled over the Centro District, each guarded by a Borgia Captain. By 1503, Ezio Auditore da Firenze had burned down all of the Borgia's towers, as well as having reopened most of the shops and re-established the Rosa in Fiore, and in turn, the Courtesans Guild, in order to aid him in his war against the Borgia.
The Centro district is the home of famous Roman landmarks, which include the Pantheon, the Mausoleo di Augusto and the Campidoglio. It is also where Tiber Island, the Assassins' stronghold, was located. Across the river, the area is known as Trastevere, which was a dilapidated area that housed many people from the Jewish community.
Centro is the only district that is adjacent to all three other districts – the Tiber river separates it from the Vaticano District, but it can be accessed via the Ponte Sant'Angelo or by gondola. Within this district, the following could be found:
- The Rosa in Fiore
- The Assassins Guild on Tiber Island
- Three Faction buildings
- Six banks
- Eight blacksmiths and one blacksmith shop quest
- Twenty-three doctors and one medical shop quest
- Six tailors and one tailor shop quest
- Five art merchants and one art merchant shop quest
- Five Borgia/Assassin Towers
- Eight pigeon coops
- Five tunnel entrances
- Three stables
- Mausoleo di Augusto
- Palazzo Senatorio
- The Centro district was the only district that did not feature any lairs of Romulus.