The Uruguay international sustained a ruptured anterior cruciate ligament during Spurs' 4-1 defeat at Leicester on February 11.
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His club confirmed the injury two days after, saying they expected Bentancur to be out for the remainder of the season.
However, Sky Sports are now reporting that the 25-year-old won't be back in action for another nine months at the earliest after he had surgery earlier this week.
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Bentancur, who joined Spurs from Juventus last summer, has been a key player for Antonio Conte's men this term.
He has already made 44 appearances for the north London club, scoring six goals and providing six assists.
Bentancur's absence is a huge setback in Spurs' fight for a top four finish, with fifth-placed Newcastle just a point behind them and possessing a game in hand on Conte's men.
With Yves Bissouma also injured and Pierre-Emile Hojbjerg suspended for their Champions League first leg clash at AC Milan, Conte was forced to field Oliver Skipp and Pape Matar Sarr in midfield.
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However, the pair failed to impress as Spurs stumbled to a 1-0 defeat at the San Siro.
Bentancur's injury diagnosis comes during a hectic fixture schedule with Spurs playing six matches in the space of 20 days.
Their Premier League clash at home to Chelsea on Sunday is followed by a trip to Sheffield United in the FA Cup on Wednesday.
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They then go to Wolves on March 4 before facing Milan on March 8. Spurs then take on Nottingham Forest on March 11 before travelling to Southampton on March 18.