Sampdoria and their starlet Mauro Icardi hope to cause another upset when Milan’s young trident comes to Marassi.
The Blucerchiati caused perhaps the shock of the season when they fought back from a goal down to win 2-1 away to Juventus despite playing with 10 men for an hour.
Gaetano Berardi was sent off in Turin and therefore suspended for this game, while Enzo Maresca, Maxi Lopez and Nicola Pozzi are injured.
Argentine teenage talent Icardi bagged a brace against Juve and starts alongside Eder.
Milan were knocked out of the Coppa Italia by Juventus on Wednesday and could feel fatigue after going to extra time in that quarter-final.
Giampaolo Pazzini is suspended against his former club, while Daniele Bonera, Mario Yepes, Sulley Muntari, Luca Antonini, Djamel Mesbah and Nigel De Jong are on the treatment table.
M’Baye Niang, Stephan El Shaarawy and Bojan Krkic are in a young trident whose combined age is 60.
Milan’s record in Genoa is not great, as they are without a victory here in six years.
There has been a change in the officials, as goal line referee Paolo Valeri has been replaced by Massimiliano Irrati.
Sampdoria: Romero; Gastaldello, Palombo, Costa; De Silvestri, Obiang, Kristicic, Poli, Estigarribia; Icardi, Eder
Milan: Abbiati; De Sciglio, Zapata, Mexes, Constant; Montolivo, Ambrosini, Boateng; Niang, Bojan, El Shaarawy
Think you know your Italian football? Share your knowledge, tips and comments to win cash prizes in OLBG's World Cup tipster competition  - £10,000 to be won!