Santino retaliates by destroying John's house with a grenade launcher. John survives and travels to the Continental Hotel in New York City where Winston reminds John that if he rejects the marker, he will be violating one of the two unbreakable rules of the underworld: no killing on Continental grounds, and honoring every marker.

John reluctantly accepts his commitment and meets with Santino, who tasks him with assassinating his sister, Gianna, so he can claim her seat at the 'High Table', a council of twelve high-level crime bosses. Santino sends Ares, his mute bodyguard, to observe John's mission. In Rome, Italy, John infiltrates Gianna's coronation and confronts her in a dressing room. Faced with certain death, Gianna chooses to take her own life by slitting her wrists. As Gianna dies, John shoots her in the head to fulfill the marker. As John leaves, Gianna's bodyguard, Cassian, recognizes John and upon realizing that he was sent to kill Gianna, attacks him. John flees to the catacombs, where he is double-crossed by Ares and Santino's henchmen, who intend to tie up 'loose ends' by killing him. After killing most of the henchmen, John is again pursued by Cassian. Their fight leads them into the reception area of the Rome Continental Hotel, which, like the New York Continental, prohibits conducting any 'business' on its grounds.

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