He suffered the injury in the fourth quarter of Wednesday's game against the Detroit Pistons.
Center Marc Gasol (left hamstring) and Norman Powell (left shoulder) are also considered out indefinitely, which removes three key players from the Raptors rotation.
While depth is a major issue going forward, especially in the frontcourt, losing Siakam for any amount of time is the biggest concern for this squad.
The 25-year-old was the league's Most Improved Player last season and might be more deserving of the award this year after turning himself into one of the best big men in the NBA.
He exited the victory over the Pistons averaging 25.1 points, 8.0 rebounds, 3.6 assists, 1.0 blocks and 1.0 steals this season. He has become more aggressive offensively and is shooting a career-high 39.2 percent from three-point range.
This comes after he was already one of the most efficient players in the league last year while averaging 16.9 points and 6.9 rebounds. He ranked 16th in the NBA with 9.3 win shares for a squad that eventually took home an NBA title.
Many expected Toronto to take a step back this year with Kawhi Leonard leaving for the Los Angeles Clippers in free agency, but Siakam's production has kept the squad among the best in the Eastern Conference. It entered Thursday with a 19-8 record.
The latest run of injuries will put more pressure on Kyle Lowry and Fred VanVleet, with Serge Ibaka likely taking on a bigger role down low.