- "For we wrestle not against flesh and blood, but against principalities, against powers, against the rulers of the darkness of this world, against spiritual wickedness in high places. Wherefore take unto you the armor of God, the shield of faith, wherewith ye shall be able to quench all the fiery darts of the wicked."
- ―A cardinal praying in St. Peter's Basilica.[src]
As such, cardinals were easily recognizable from the rest of the crowd by their red or white clothes, and by their headwear; which included a scarlet galero (a wide brimmed hat), a zucchetto (a small skullcap) or a biretta (a cap with four peaks).
In the 15th and 16th centuries, certain cardinals were allied to the Borgia, and aided them in their control of Rome. In order to gain their support, Cesare Borgia paid for the appointment of several of them.
Juan Borgia was appointed into his position as cardinal by his uncle, Pope Alexander VI. Upon being established as "the Banker," he paid for and managed the expenses of Cesare's military exploits. However, he was also corrupt and wasteful, using his resources to throw lavish Pagan parties. During one such celebration, he was assassinated by Ezio Auditore da Firenze.
A cardinal also relayed Borgia orders to the corrupt leaders of the Followers of Romulus, instructing them on how to control those under them. He also wrote sermons for the leaders to deliver, in order for the Pagan group to be manipulated, and terrorize the citizens of Rome for the Pope's gain.
In 1503, upon his fall from power, Cesare attempted to rally aid from several cardinals, whose appointment he had previously paid for. However, they only said that they supported the election of the new Pope, Giuliano della Rovere, and that Borgia money had become tainted.
- Cesare's brother Juan wore the attire of a cardinal in Assassin's Creed: Ascendance, despite being Captain General at the time.
- Cesare was made a cardinal at age 18, but he never wore the relative vestment in any Assassin's Creed media.
- Some Cardinals disliked the Borgia in the memory a Wolf in Sheep's Clothing, which they opposed their tyranny and hoped that Ezio would free Rome from the Borgia so that the Church would be restored to its former glory which he ultimately did.
- In Assassin's Creed: Project Legacy, despite certain memories involving Pope Alexander VI, the supporting image instead showed someone dressed as a cardinal. Among these were "All Ears" and "Religion."