Hoping to rebound from a tough loss to the Patriots, the Bills would play their Week 2 home opener in an interconference duel with the Tampa Bay Buccaneers. This would be the first time that Buffalo ever hosted Tampa Bay in a regular season game, having played a preseason game with each other in 1977. In the first quarter, the Bills came out firing as quarterback Trent Edwards completed a 32-yard touchdown pass to wide receiver Lee Evans, safety Donte Whitner returning an interception 76 yards for a touchdown and kicker Rian Lindell making a 31-yard field goal. The Buccaneers would get on the board in the second quarter as quarterback Byron Leftwich completed a 42-yard touchdown pass to tight end Kellen Winslow, while Buffalo replied with Lindell getting a 43-yard field goal. Tampa Bay would close out the half as Leftwich completed an 8-yard touchdown pass to running back Carnell "Cadillac" Williams. After a scoreless third quarter, the Bills began to pull away as Lindell got a 43-yard field goal and Edwards completed a 43-yard touchdown pass to wide receiver Terrell Owens. The Buccaneers tried to rally as Leftwich completed a 6-yard touchdown pass to tight end Jerramy Stevens (with a failed two-point conversion), yet Buffalo closed out the game with Lindell nailing a 20-yard field goal. With the win, the Bills improved to 1-1.. In which quarter were no points scored?