The next week Cromartie made his first NFL start in place of the injured Quentin Jammer and intercepted three passes thrown by Peyton Manning of the Indianapolis Colts; the last of which was a leaping one-handed interception in front of Colts WR Reggie Wayne. Cromartie called the interception the best play of his short career. He is the first player to intercept Peyton Manning three times in one game during the regular season, and earned Defensive Player of the Week honors for his performance in the game.