The flag of Spain is incorrectly depicted as the Bars of Aragon with the Coat of Arms of Castile and Leon superimposed. The actual Spanish flag at the time consisted of the arms of Castile, Leon and Aragon quartered, along with those of Sicily and recently conquered Granada as well.
The Spanish ambassador uses the word America in reference to the lands discovered by Columbus. However, this term was not coined until the elaboration of the Waldseemüller map in 1507, four years after the death of Pope Alexander VI.
Lucrezia speaks of "sprezzatura", yet the concept would not become known until twenty five years after her father's death with the publication of 'The Book of the Courtier' by Baldessare Castiglione in 1528.
Lucrezia asks Cesare how Prince Djem died and he replies "swamp fever", to which Lucrezia comments about Djem being brought down by a mosquito, which indicates malaria. The transmission of malaria by mosquito wasn't discovered until hundreds of years later in the 1880s.
Savonarola claims to have dreamed about a Pope "blackened by syphilis". While some historians believe that the disease was already known in 1493 Italy, the word syphilis was not coined until the publication of Fracastoro's poem Syphilis sive morbus gallicus ("Syphilis or The French Disease") in the 1550s, which is about a shepherd named Syphilus that gets the disease as punishment for insulting the Sun god.