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Inter have Marcus Thuram back with Lautaro Martinez and Carlos Augusto, while AC Milan return Adrien Rabiot behind Rafael Leao and Christian Pulisic in the Derby della Madonnina.
It kicks off at San Siro at 19.45 GMT.
You can follow all the build-up and action as it happens from today’s Serie A games on the Liveblog.
This is not just a bitter local rivalry, but also a head-to-head for the top of the table, as the Scudetto race looks to be tighter than ever this season.
Both sides have injury problems to deal with and some good news from the treatment room too.
Denzel Dumfries has not recovered from an ankle issue on international duty, so joins Henrikh Mkhitaryan, Raffaele Di Gennaro and Tomas Palacios in the stands.
Carlos Augusto is shuffled over to the right flank to cover rather than Luis Henrique, while Petar Sucic is preferred to Piotr Zielinski in midfield.
Thuram returns to the starting XI for the first time since September 30 to partner Lautaro Martinez, and Francesco Acerbi gets the nod rather than Yann Bisseck.
Max Allegri experiences his first Derby della Madonnina for the first time since 2013, his most recent stint on the Milan bench.
Santiago Gimenez has still not shaken off that ankle problem, while Zachary Athekame is also ruled out by a soleus injury.
The good news for Allegri is that Pulisic, Rabiot and Fikayo Tomori are all fit for a return to the starting XI, with Rafael Leao still getting accustomed to his more central attacking role.
Davide Bartesaghi is preferred to Pervis Estupinan on the left flank.
Rabiot has not played since the 0-0 with Juventus on October 5, so reunites with Luka Modric for an experienced midfield pairing.
Inter have managed only two draws in the last five competitive meetings with Milan between Serie A, the Coppa Italia and Supercoppa Italiana.
Inter: Sommer; Akanji, Acerbi, Bastoni; Carlos Augusto, Barella, Calhanoglu, Sucic, Dimarco; Thuram, Lautaro Martinez
Milan: Maignan; Tomori, Gabbia, Pavlovic; Saelemaekers, Fofana, Modric, Rabiot, Bartesaghi; Pulisic, Leao
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