Coach Mike Brown said O'Neal will miss the Cavs' game Friday night at Toronto.
"I don't know how long Shaq will be out," Brown said after the 108-88 victory over Boston. "He'll see the doctor and it will go from there."
Brown could not say how O'Neal was hurt, but it appeared to be when Glen "Big Baby" Davis blocked his shot with just over 7 minutes left in the first half. The Cavaliers called a timeout soon after to take O'Neal out of the game, and they later issued an injury report saying he had a "significant right thumb sprain" and would not return.
O'Neal was not available for comment after the game.
"We need him out there," Cavaliers forward LeBron James said. "We play faster without Shaq in the lineup ... but in the playoffs you can't play fast all the time. You need to establish the half-court offense. That's what he does for us."
His absence is even tougher to overcome because the Cavaliers traded backup center Zydrunas Ilgauskas to Washington before the trade deadline. Ilgauskas was waived Thursday and could re-sign with the Cavs next month.
O'Neal had six points and two rebounds before leaving.