It's not just the fact that the Patriots (9-5) seem headed for the playoffs while the Bills (5-9) are out of contention and looking ahead to next year. It's also the fact that Patriots quarterback Tom Brady has a 29-3 career record against Buffalo and Patriots head coach Bill Belichick is 33-4 against the Bills. And that includes a 25-6 New England victory when the teams met in Buffalo earlier this season.
Plus, the Patriots should be more motivated. A win over the Bills or a Miami loss to Jacksonville will clinch a 10th straight division title for New England.
However, the Patriots have lost two in a row, and Bills rookie quarterback Josh Allen did not play in the earlier game against New England.
Allen provides a different dimension, as he showed in two games earlier this month. He rushed for 135 yards in a 21-17 loss to Miami on Dec. 2, and ran for 101 yards in a 27-23 loss to the New York Jets two weeks ago.
He cut back on the running in last week's 14-13 victory over the Lions, but the 6-foot-5, 237-pound rookie still offers a run threat.
"You've just got to man up," Patriots safety Patrick Chung said, regarding tackling Allen. "You've just got to tackle him. He's just like a running back or a tight end or someone who we're trying to tackle anyway. Regardless of how good the quarterback is running, you're still going to tackle him. So you don't go about anything differently. You just go out there and just play."
Allen's passing has been mediocre. He has completed more than half his passes only once in the past four games, and he has thrown four interceptions and three touchdown passes in that span.
Allen has a big-play threat at his disposal in wide receiver Robert Foster, who leads the NFL with an average 24.6 yards per catch
"It's another opportunity for Josh to grow and develop," said Bills head coach Sean McDermott. "Now it's on the road against a very good football team, against a defense that he didn't face the first go around. All that will be somewhat new, but will provide him an opportunity to take another step in his development, his growth and then our offense's growth as well."
Allen may be the biggest running threat on Sunday for the Bills, who have not had much of a ground game this season but need to run the ball against a Patriots defense that has given up 347 rushing yards over the past two weeks.
The Bills' top running back, LeSean McCoy, is questionable again with a hamstring injury, and the status of Chris Ivory is uncertain too because of a shoulder problem. That might mean Keith Ford will get extended work against New England, one week after he made his NFL debut, when he rushed for 46 yards.
"Coach always says be ready, your name can be called at any time," Ford said. "Be ready, stay in the game plan, so just from the start I made it happen, just make a routine and keep preparing for the week."
Whether the Bills can be ready for Brady and the Patriots' attack is another question.
Brady has not been quite as efficient as he was last season when he was named the league's MVP. He has already thrown nine interceptions, and he has not thrown more than that in an entire season since 2013.
And New England only managed 10 points in last week's 17-10 loss to Pittsburgh. Brady ranks only 14th in the NFL in passer rating.
McDermott dismisses the notion that the 41-year-old Brady is on the decline.
"No, to me, he looks even better than he has in years past, believe it or not," McDermott said. "I know that the numbers may not support that, but I think his game is strong, he doesn't turn the ball over. I think he's as good as ever. Well, the way he's allocating the ball to different receivers, how he's getting them in and out of plays, how they use the no-huddle offense strategically. I think all of that really showcases his ability, not only with his arm physically but also his mental capability."
The last time these teams met, Brady did not throw any touchdown passes but he amassed 324 passing yards and led his team to a victory over a Bills team that had Derek Anderson as its starting quarterback.