"Balotelli won't play against Lazio, he has internal bruising and he isn't available," coach Massimiliano Allegri told Milan's official TV station Milan Channel. "He's been out of action for a week and can't play."
Allegri later told reporters that the striker was "99.9 per cent" certain to not play.
Balotelli took a knock to his right knee when he clashed with Inter Milan goalkeeper Samir Handanovic in last Sunday's game, which finished 1-1.
Saturday's match is important in the race for the third Champions League place, with Lazio third on 47 points and Milan two points behind them in fourth.
Balotelli has scored four goals in four games for Milan since signing from Manchester City in the January transfer window.