The pair are separated by just a point, with Milan and Ajax on eight and seven respectively, while Barcelona in first place are guaranteed a spot in the knockout stages.
Milan could finish in first place, however, if they beat Ajax and Barca suffer an unlikely defeat at home to Celtic.
Stephan El Shaarawy has returned from injury recently and could start after appearing from the bench in Milan's last two Serie A games.
Dutch champions Ajax, meanwhile, head to Italy knowing that only a win will be good enough to see them reach the last 16.
Bojan Krkic, who spent last season on loan with Milan, could start for the visitors but is likely to begin on the bench.
The reverse fixture between these two teams back on October 1 was a dramatic affair as both sides scored late on in a 1-1 draw.
Possible starting lineups
Milan: Abbiati; Poli, Mexes, Zapata, Emanuelson; Montolivo, De Jong, Nocerino; El Shaarawy, Balotelli, Kaka
Ajax: Cillessen; Van Rhijn, Veltman, Moisander, Ligeon; Klaassen, Blind, Serero; Schone, Hoesen, Fischer
Sports Mole says: 2-0