The Eastern Conference champion Cavaliers fell just short in their season opener thanks to a big defensive stop from Pau Gasol.
Gasol blocked a LeBron James layup that would have tied the game just before the buzzer, preserving a 97-95 win for the Bulls over the Cavs.
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The block was Gasol's sixth of the night, as the Bulls got a little revenge on the Cavs for knocking them out in the second round of last season's playoffs.
Jimmy Butler knocked away the ensuing inbound pass to seal the victory.
James scored 25 points and grabbed 10 rebounds in the loss for the Cavs.