In week 13, the Lions hosted the Indianapolis Colts. They started the scoring when Jason Hanson kicked a 48-yard field goal. The Colts responded with a 17-yard touchdown catch by Donnie Avery from Andrew Luck. Detroit replied when Brandon Pettigrew caught a 16-yard touchdown pass from Matthew Stafford, and added to their lead in the second quarter when Mikel Leshoure ran in a touchdown from 6 yards out. The Colts scored their only points of the second quarter when Coby Fleener caught a 26-yard touchdown pass from Andrew Luck. The Lions closed out the half with 2 field goals from Jason Hanson from 33 and 52 yards out respectively. Each team scored a touchdown in the third quarter. First the Colts' Vick Ballard ran one in from 11 yards out, then Detroit's Calvin Johnson caught 46-yard touchdown pass from Matthew Stafford. The Lions' only points of the final quarter was a 31-yard field goal by Jason Hanson. The Colts then rallied from behind with two touchdowns. First LaVon Brazill caught a 42-yard pass from Andrew Luck, then Donnie Avery caught a 14-yard pass from Andrew Luck in the final seconds of the game for the win. It was the Lions' third consecutive loss in which they were leading with less than 2 minutes left in the game.

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