Alessandro Matri faces his former club, as a Milan team in crisis visits Fiorentina targeting third place.
It kicks off at 19.45 GMT, click here for a match preview.
The Viola have the chance to do The Double over the Rossoneri, having already won at San Siro earlier this season.
They have Napoli in their sights after a victory at the San Paolo on Sunday, which put the Europa League exit behind them.
However, Vincenzo Montella is dealing with an injury crisis that has ruled out Mario Gomez, Giuseppe Rossi, David Pizarro, Juan Manuel Vargas, Marvin Compper, Ante Rebic and Anderson.
It means Matri faces his former teammates, having left Milan on loan in January with just one goal to his name.
Joaquin and Juan Cuadrado support him with another ex-Milan man, Massimo Ambrosini, in midfield.
Milan are struggling badly, as a 1-1 draw at Lazio on Sunday ended their run of four consecutive defeats in all competition.
The team has spent the last few days in a Roman training camp to prepare for this game with CEO Adriano Galliani standing by under-fire Coach Clarence Seedorf.
They too have several absentees, as Andrea Poli is suspended with Mattia De Sciglio, Stephan El Shaarawy and Ignazio Abate injured.
Mario Balotelli returns to the starting XI after he was dropped against Lazio, partnering Kaka, Keisuke Honda and Adel Taarabt.
Milan are unbeaten in their last seven trips to Florence in all competition, but haven’t beaten the Viola home or away in the last five meetings.
Fiorentina: Neto; Tomovic, Savic, Gonzalo; Pasqual, Ambrosini, Borja Valero, Matias Fernandez, Cuadrado; Matri, Joaquin
Fiorentina bench: Rosati, Lupatelli, Roncaglia, Diakite, Bakic, Wolski, Aquilani, Ilicic, Matos, Venuti, Fazzi
Milan: Abbiati; Mexes, Rami, Bonera, Constant; De Jong, Muntari; Kakà, Honda, Taraabt; Balotelli
Milan bench: Amelia, Gabriel, Robinho, Pazzini, Saponara, Birsa, Essien, Zapata, Cristante, Silvestre, Emanuelson, Zaccardo