The 30-year-old has not featured for the Bundesliga outfit since the club's 4-0 defeat to Wolfsburg in August, when the Netherlands international picked up ligament damage in his right knee.
Jens Keller had hoped to have Huntelaar available after the international break, but a training injury on Monday has curtailed his progress.
And Schalke must now wait to see if an operation will be required to correct the issue.
A statement on the club's website read: "Klaas-Jan Huntelaar suffered deterioration in his right knee after a training incident on Monday.
"This resulted in the 30-year-old having an MRI examination on Tuesday.
"Whether the injury is treated conservatively or surgery is necessary, all parties will decide in the coming days."
Prior to his injury, the Dutchman had netted three goals in as many games for the Gelsenkirchen outfit, who sit eighth in the Bundesliga ahead of Saturday's trip to Eintracht Braunschweig.
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