Miller appeared to bend his knee awkwardly after he had his foot stepped on as he tried to get to Lions quarterback Jared Goff.
The Pro Bowl outside linebacker was able to limp off but spent time in the medical tent before being carted to the locker room.
Bills head coach Sean McDermott was unclear about the extent of Miller's knee issue, which forced him out of the game with less than three minutes left in the first half.
"I don't know," McDermott told reporters when asked about Miller's status. "I only connected with [head athletic trainer] Nate [Breske] at half-time, so I don't have anything to give you on that."
Miller was spotted leaving the X-ray room at Ford Field but was not wearing a moon boot nor using crutches.
The 33-year-old, who joined the Bills in the offseason from the Los Angeles Rams, has a team-high eight sacks this season. He entered Week 12 ranked second in the NFL with 37 pressures.