Sensational rookie Andrew Luck and the Indianapolis Colts will wind up the biggest winners of Week 10 if they can avenge their September loss to the Jacksonville Jaguars.
At 5-3, the Colts are already the NFL's No. 1 surprise story this season. But at 6-3, Indy would be just a handful of wins away from the playoffs, completing the one-year transition from worst team in football to postseason contender.
But not everyone can be a winner in Week 10.
Here we forecast some of this coming weekend's biggest winners and losers.
The entire AFC West will be on the road in Week 10, which bodes well for the division's top team, the Denver Broncos, who will travel to Carolina to take on the Panthers.
Carolina is just 2-6 this season and has won just one of four home games. Although the Panthers' secondary hasn't been terrible in 2012, it has yet to face a scorching-hot Manning. The veteran passer has more than 2,400 passing yards and 20 touchdowns just halfway through the year.
I predict a Broncos win, which will move Denver to 6-3 and keep it atop the division. A Chargers loss in Tampa Bay would be icing on the cake and give the Broncos a two-game lead heading into Week 11.
Arizona is the only NFC West team on a bye in Week 10, and boy do the Cardinals need a week off. After a brilliant 4-0 start to the year, they are in the midst of a five-game losing skid.
Not only are the Cards guaranteed not to lose this weekend, but division-leading San Francisco will host St. Louis, and second-place Seattle will be home against the New York Jets. If the Rams can find a way to beat the 49ers, then Arizona will return to the field in Week 11 just two games out of the division lead.
Though a Rams' win isn't likely, the simple fact that the Cardinals can regroup and breathe this week is a monumental win for them.
I'm not sure who's responsible for scheduling Week 10's Monday Night Football matchup, but they should be punished. The surging Pittsburgh Steelers will host the reeling (and I mean reeling) Kansas City Chiefs in prime time on Monday.
Let that sink in for a minute.
The Steelers have won three straight while the Chiefs have dropped their last five games. And oh yeah, Kansas City hasn't held a lead in regulation at any point this season and sports a minus 20 turnover differential.
This game is sure to be must-miss television even for die-hard NFL fans. Pittsburgh is a lock to win in Week 10. The only hard part will be watching.
Leslie Frazier's team has lost two in a row and three of its last four overall. That's bad news in Week 10 since the Vikings will host a hot Detroit Lions team that will be looking to avenge its Week 4 home loss to Minnesota.
The Lions have won two in a row and three of their last four games. With the Green Bay Packers on a bye week and the NFC North-leading Chicago Bears set to face a stiff challenge in the Houston Texans in Week 10, I predict the Lions will be motivated to make up ground in the division and will roar to a road win on Sunday, sending the Vikings to their third straight defeat.
Minnesota needs to find offense from somewhere other than Adrian Peterson. Until then, the Vikings will continue to struggle and wind up one of Week 10's biggest losers.
Follow Bleacher Report Featured Columnist Patrick Clarke on Twitter.