The Spanish Assassins were the Brotherhood of Assassins located in Spain, who were, during the Renaissance, closely tied with the Spanish royal house and the enemies of Templar-influenced inquisitors, who massacred the Assassins across the country.
In 1491, Tomás de Torquemada was fooled by Rodrigo Borgia, the Grand Master of the Templar Order, into believing that the Assassins were heretics. As a result, the Spanish Inquisitors arrested and burned numerous Spanish Assassins. Luis de Santángel, an Assassin and companion of Christoffa Corombo, informed the Italian Assassin Ezio Auditore da Firenze of the Inquisition, which caused Ezio to sail for Spain. The spokesman of the Spanish Assassins, Raphael Sánchez, met with Ezio, and assigned him to kill several high-ranking Inquisitors. With help from other Spanish Assassins, Ezio rescued several captured Brothers, and killed many Inquisitors. He failed to kill Tomás de Torquemada however, and later spared him, saying that he was not a Templar, just blinded by his faith.
However, the Inquisition killed most of the Assassins, although they managed to kill Torquemada in 1498. By that same year, Santángel had died, leaving the Assassins with no grip on the Spanish royal family and the branch nearly deserted. Ezio, now co-leader of the Italian Assassins along with Niccolò Machiavelli, sent his apprentices to reorganise the branch.
These apprentices, searched Santángel's room, found his journal, and realized that he had been slowly poisoning Queen Isabella. They felt at first that it was retaliation for slaughtering his family. However they kept an eye on the Queen, and found that she was threatened by the Borgia to help spread the Inquisition. They decided to finish what Santángel started, poisoning the Queen. They found the recipe of the poison, and doubled the dose to ensure her death. They found that one of the Queen's servants was a collaborator, and through her, they administered a fatal dose.
By 1511, the Spanish Assassins had regrouped and occasionally received aid from Turkish Assassins sent from Constantinople by Ezio Auditore. This year, the Spanish Assassins once again faced problems from the Inquisitors, who were now acting on orders of Francisco Jiménez de Cisneros. With help of the Ottoman Assassins, the Spanish Assassins eliminated the culprits.
- The Spanish Assassins encountered by Ezio in Assassin's Creed II: Discovery bore a remarkable resemblance to the mercenaries of Italy and Constantinople.