The Schalke striker suffered an injury at the weekend against Wolfsburg which will see him miss the side's clashes with PAOK for a group stage spot
The Netherlands international was withdrawn at half-time during Saturday's 4-0 Bundesliga defeat to Wolfsburg after a collision with opposition goalkeeper Diego Benaglio.
It means that the Bundesliga side, who have drawn and lost in their opening two games of the season, will be without their star striker against PAOK - coached by former Veltins Arena boss Huub Stevens - in the must-win matches to decide who will reach the group stage.
Their form will need to improve if they are to eliminate the Greek club and doing so without Huntelaar will be a big ask, with the 30-year-old having proved a vital source of goals for Schalke since his arrival in August 2010.
Huntelaar has netted 80 goals in 119 appearances for Jens Keller's men, including 21 in 27 European outings.