Federico Chiesa returns with Cristiano Ronaldo and Alvaro Morata as Juventus are practically in a play-off with Zlatan Ibrahimovic and Brahim Diaz’s Milan.
It kicks off in Turin at 19.45 UK time (18.45 GMT).
This is essentially a play-off for Champions League football and therefore an extraordinarily important showdown for both this season and their future.
They went into the weekend locked together in second place with Atalanta, and just two points clear of Napoli, but both those teams won already.
Giorgio Chiellini is surprisingly chosen to partner Matthijs de Ligt, leaving Leonardo Bonucci on the bench against his old club.
The good news is the return of Chiesa, who missed the last three games with an injury.
He is thrown straight into the starting XI with Ronaldo and Morata, sending Paulo Dybala to the bench, while Adrien Rabiot and Weston McKennie play in midfield.
Milan have Samu Castillejo suspended and Daniel Maldini injured, so Brahim Diaz gets the nod with Alexis Saelemaekers and Hakan Calhanoglu in support of Zlatan Ibrahimovic.
Both Ante Rebic and Rafael Leao are dropped after recent poor performances, with former Juventus star Mario Mandzukic also back on the bench following injury.
Milan have lost each of their last nine Serie A visits to the Juventus Stadium, but the Bianconeri haven’t kept a clean sheet in 10 games this season.