Visiting Sampdoria stunned AC Milan 1-0 in its opening Serie A match on Sunday through Andrea Costa's headed goal in the 60th minute.
Kevin-Prince Boateng almost rescued a point for Milan in stoppage time but his effort crashed off the right post.
Milan midfielder Mathieu Flamini could also have scored in a frantic finale but his effort was cleared off the line by Sampdoria defender Daniele Gastaldello.
The result marks a memorable start for promoted Sampdoria and new coach Ciro Ferrara, whereas Milan has until Friday to bring in reinforcements before the transfer window closes.
Milan was jeered off the pitch by its fans after the game, while the Sampdoria players stayed behind to soak up the applause from their travelling supporters.
The Rossoneri already find themselves on the back foot, after defending champion Juventus beat Parma 2-0 on Saturday and Napoli beat Palermo 3-0.
A breathtaking goal from Pablo Osvaldo was not enough to give Roma all three points, as it was held to a 2-2 draw at home by Catania in Zdenek Zeman's return to the Roma coaching post after a 13-year absence.
It was Milan's first game without star strikers Zlatan Ibrahimovic and Antonio Cassano as well as key defender Thiago Silva, who were all sold during the off-season.
Club icons Alessandro Nesta, Clarence Seedorf, Gennaro Gattuso and Filippo Inzaghi left the club at the end of last season, along with Mark Van Bommel and Gianluca Zambrotta.
The San Siro also featured banners berating Cassano, who moved to bitter rival Inter Milan on Wednesday in a swap deal for Giampaolo Pazzini.
Milan was also hampered by the absences of captain Massimo Ambrosini, Ignazio Abate, Alexandre Pato, Sulley Muntari and Rodney Strasser through injury.
The game almost got off to a perfect start for the visitors when Eder took advantage of a glaring error by Daniele Bonera and raced toward goal. However, Bonera atoned for his mistake and did well to clear the danger and avoid conceding a penalty.
Seconds later, Boateng should have scored but failed to control the ball and Sampdoria goalkeeper Sergio Romero was able to gather.
Milan struggled to create any meaningful chances and looked dangerously exposed at the back.
Robinho had two good chances after the break, but his effort landed on the roof of the net and then Romero did well to save another long-range effort from the Brazilian forward.
Pazzini made his debut in the 57th minute, but it was his former club that took the lead moments later.
Costa rose highest in the area to powerfully head a corner into the bottom left of the net with goalkeeper Christian Abbiati rooted to the spot.
Milan's chances of an equalizer dipped when Robinho limped off the pitch and was replaced by Urby Emanuelson.
The hosts thought they had levelled five minutes later, but Romero parried Yepes' header onto the post from point-blank range and grabbed the ball just as it was about to go over the line.
Kevin Constant almost scored with five minutes to go, on his Milan debut, but he fired straight at Romero from close range.
In Sicily, Napoli should have taken the lead in the 41st when Christian Maggio headed to Edinson Cavani, who was all alone a few yards out from goal. But the Uruguayan's effort crashed off the underside of the crossbar and out of danger.
Napoli went in front in first-half stoppage time when Maggio raced down the right flank and cut the ball across to Marek Hamsik, who controlled it well before unleashing a fierce shot into the top right corner.
Maggio doubled Napoli's lead 10 minutes from time following a long ball from Hamsik, before Cavani headed in a third late on.
Inter Milan cruised to a 3-0 win over promoted Pescara thanks to goals from Wesley Sneijder, Diego Milito and Philippe Coutinho. Cassano provided the assist for the second goal on his debut.
In the capital city, Giovanni Marchese's goal for Catania should have been ruled out for offside. But Roma was back on level terms when Osvaldo — who had headed onto the post two minutes into the second half — scored with a stunning overhead kick that looks certain to be one of the main contenders for goal of the season.
Alejandro Gomez restored Catania's lead, but 18-year-old Nicolas Lopez levelled in stoppage time on his debut only moments after coming off the bench.
Lucas Castro almost won the game for Catania but he hit the crossbar.
Elsewhere, Chievo beat Bologna 2-0 and Genoa won by the same score against Cagliari, while promoted Torino held Siena to a scoreless draw.
Hernanes' 17th-minute goal was enough to give Lazio a 1-0 win at Atalanta.