The 30-year-old Holland international had a scan on Tuesday to reveal the extent of the damage - an aggravation of a previous knee ligament injury - and can now expect to be absent for several more weeks just as he was closing in on a comeback.
"It's incredible. How unlucky can one be?" coach Jens Keller said to the Bild newspaper after the Dutchman was helped off the field by team-mates.
"I have no idea what we're doing wrong."
Huntelaar said it was "just an unfortunate collision".
Luck has not been on his side lately. After tearing ligaments in his right knee in August, he was expected to miss just a month, but a series of setbacks during his recovery doubled that to two months.
This latest knock has further aggravated that same injury, and a decision will be taken in the coming days as to whether he will undergo an operation or if more conservative methods are to be used, according to a statement on the Gelsenkirchen club's website.
Either way, Huntelaar will miss Schalke's Champions League tie with Chelsea next Tuesday as well as the derby against Borussia Dortmund the following weekend.