The Bills are trying to re-establish their C.J. Spiller/Fred Jackson-led rushing attack, and just in time to face the 49ers' stingy run defense. San Francisco will take advantage of a injury-riddled Bills offensive line and force Buffalo to be one-dimensional, making Ryan Fitzpatrick try to win it through the air. He'll struggle, and San Fran will win easily.
Prediction: 49ers 28, Bills 10
Buffalo had little time to recover from its second-half meltdown against New England last week as it head into San Francisco, where the 49ers have won their last seven regular season games. San Fran has been a force on defense, the topper coming last week in their shutout victory against the Jets. An ailing backfield and a turnover-crazed Fitzpatrick will have a hard time against the league's third-ranked defense, and it will be a statement game for the Buffalo defense against a stout rushing tandem.
Prediction: 49ers 21, Bills 10
Prediction: 49ers 27, Bills 3
Prediction: 49ers 31, Bills 21