Adel Taarabt and Adil Rami got the goals which saw Clarence Seedorf get one over on former teammate Sinisa Mihajlovic. Maxi Lopez saw red for the Blucerchiati, during a heated second half.
Seedorf and Mihajlovic shared a dressing room during their playing days at Sampdoria back in 1995-96. The hosts came into this game without suspended pair Lorenzo De Silvestri and Daniele Gastaldello.
Milan were decimated by injuries. Christian Abbiati, Daniele Bonera, Mattia De Sciglio, Cristian Zapata, Matias Silvestre, Valter Birsa, Robinho, Stephan El Shaarawy, Bryan Cristante and Mario Balotelli all missed out. Giampaolo Pazzini started against his former club
Milan fashioned the game's first chance after seven minutes. Shkodran Mustafi headed off the line after Keisuke Honda had threaded through for Pazzini to hook his shot over an advancing Junior Da Costa.
The Rossoneri did hit the front five minutes later. Da Costa spilt Taarabt's header from Rami's cross and the on-loan QPR midfielder slotted in the rebound for his second goal in a Milan shirt. Replays showed Da Costa perhaps should have caught the initial effort.
Samp were somewhat stifled going forward. They fashioned a chance on 26 minutes through Manolo Gabbiadini. However, the winger's shot lacked power as it went past a sea of players into Marco Amelia's gloves.
Riccardo Saponara had two chances to double Milan's advantage before half time. Honda slipped him in, but Da Costa was quick out of the blocks to narrow the angle and save at his feet. The 22-year-old then swung wildly as he latched onto Kevin Constant's low cross and volleyed over.
Roberto Soriano replaced the disappointing Pawel Wszolek for the second half, while Maxi and Andrea Poli came on to face their respective former clubs as the game wore on.
Milan doubled their lead just short of the hour, albeit thanks to a dubious decision. Da Costa collided with Pazzini's arm as he came to collect Taarabt's cross and the goalkeeper went to ground. Rami headed the ball into the empty net, as play wasn't called back. Samp players surrounded the referee appealing for an infringement, but the goal was allowed to stand.
The home side were denied a penalty midway through the second half. Maxi slotted the ball through two defenders for Eder to run clear. Amelia led with his feet and touched the ball, as Eder went over him and went to ground clutching his knee.
Samp's frustration boiled over and Maxi compounded a miserable afternoon on 72 minutes, when he was shown two yellow cards in quick succession for dissent.
Amelia pulled off a superb point blank save to deny Samp nine minutes from the end. Substitute Renan Garcia shot across goal with his first touch of the ball and Amelia stuck out his body to prevent Eder from completing a simple tap in.
Rami was denied his second goal in the final minute, as Da Costa caught his goalwards header. Eder continued to be out of luck when Amelia tipped his curling effort over the bar.
Sampdoria: Da Costa; Fornasier, Mustafi, Regini, Costa; Palombo, Obiang; (Maxi Lopez 56) Gabbiadini, Kristicic, (Renan 81) Wszolek; (Soriano 46) Eder
AC Milan: Amelia; Abate, Zaccardo, Rami, Constant; (Emanuelson 76) Montolivo, Muntari; (Essien 64) Honda, Saponara, (Poli 57) Taarabt; Pazzini
Goals: Taarabt 12 (M) Rami 58 (M)
Sent off: Maxi Lopez 72 (S)