After a heated argument with della Rovere, Rodrigo convinces Pope Innocent to name King Ferdinand and Queen Isabella of Spain, "Most Catholic Majesty". The Medici give a bankrupted Pope Innocent a loan to pay off his son's gambling debts, in return for Giovanni de Medici's seat as a Cardinal. Rodrigo reveals his intention to restore the Saint Peter's Basilica, if he becomes Pope.
Alessandro and Cesare visit a Striga to predict Cesare's future. She foresees five deaths over the course of the summer that will change Cesare's life. The Borgia, Orsini, Medici and Cibo dine together to celebrate their new alliance: Giovanni de Medici is now a Cardinal, Juan is Duke of Gandia and Maddalena de Medici is married to the Pope's son, Franceschetto Cibo.
The Conclave continues, as no single Cardinal has received enough votes to be elected Pope. Rodrigo visits della Porta, hoping to gain his votes, and outlines the consequences of what will happen depending on who is elected Pope -- war with Naples or Milan, Rome slaughtered. Rodrigo emphasizes his neutrality on these issues, making him best suited to be elected.
Cesare and Alessandro arrive in Spoleto, where Rodrigo has told them to remain, indefinitely. They meet Cesare's new secretary, Agapito Geraldini. Rodrigo is crowned Pope, announcing plans to rebuild St. Peter's, funded by an annual tithe from each Cardinal. At a celebration at the Apostolic Palace, reserved for men, Giulia enters, much to Burchard's dismay.
Spanish Ambassador De Haro announces the discovery of a New World by the legendary explorer, Cristofero Colombo. If Rodrigo grants Spain's claim legitimate, King Ferdinand will offer Princess Maria Enriques de Luna's hand in marriage to Juan. Rodrigo uses a compass, to divide the New World between Spain and Portugal, clearly favoring Spain, while appearing neutral.
At the Consistory, Carafa announces King Ferrante of Naples is dead. The Cardinals debate the rightful ruler of Naples: Ferrante's son, Prince Alfonso d'Aragona or King Charles of France. Cardinal della Rovere argues in favor of Charles, despite Rodrigo's new ties to Alfonso. The Consistory concludes, as Della Rovere leaves to inform King Charles of Rodrigo's plans to study both claims.
As Giulia gives birth, Rodrigo and the remaining Cardinals discuss the state of war. Della Rovere is poised to take over as pope. Switching strategies, Rodrigo gives Charles permission to pass through Rome.
At the French encampment, Djem learns of his son's murder by his brother, Bajazet. Distraught, he falls ill. Cesare uses the opportunity to escape and informs Lucrezia that d'Este is in a hospital in Rome. Lucrezia goes to visit him, where she learns that he is suffering from the "French Disease." Heartbroken that he has been with other women, she asks Rodrigo for permission to join the convent.
Having learned that his wife died in childbirth, an angry Juan confronts Lucrezia about her role in Maria Enriques' escape. Lucrezia is devastated, firm in her resolve to remain a nun she visits Lucia to ask how she may be "blessed" with stigmata. Cardinal Carafa reveals the people of Naples have chosen Federigo d'Aragona to be their king.
Rodrigo addresses the Cardinals. Upon receiving a letter of condolence from della Rovere, Rodrigo invites him back to Rome and dismisses Giulia. After Cesare informs him that Juan killed their halfbrother Pedro Luis, Rodrigo sends him back to Valencia. Rodrigo denies Lucrezia's request to marry Pedro Caldes. He orders her to become a nun and care for Juan's orphaned children.