Karetsas came on for Maximilian Beier in the 62nd minute of the Black and Yellows' away match at the Alte Försterei (0-0). Just a few minutes later, the attacking midfielder sustained the injury while trying to turn past Union's Rani Khedira on the edge of his own penalty area.
His leg twisted, leaving him clearly in considerable pain. During the break for treatment, Dortmund captain Nico Schlotterbeck signalled straight to the bench that Karetsas could not continue. Staff helped Karetsas off, and US prospect Mathis Albert came on in his place in the 70th minute.
"I hope it's nothing serious," Dortmund defender Waldemar Anton told Sky after the final whistle. "It looks like his foot got caught in the turf and his leg buckled a little." Another spell on the sidelines for the Greek "would really hurt us", added goalkeeper Gregor Kobel.
Khedira wished his opponent a speedy recovery: "I hope he won't be out for too long."
How did Lars Ricken and Niko Kovac react?
Karetsas' difficult weeks continue. The 18-year-old new signing made a strong impression after his 30-million transfer from KRC Genk in the summer, but he is still searching for his form following his collapse in the Champions League against FC Villarreal in early September.
"We will have to carry out further examinations to determine how serious the injury is. We can't give a diagnosis yet," said managing director of sport Lars Ricken.
Coach Niko Kovac added: "We now have to see whether it's something more serious or not. I hope it isn't, of course." He continued: "It is frustrating. Right now, I feel sorry for the lad, who certainly hasn't had much luck lately."