Both Milan clubs lost further ground on Serie A frontrunners Juventus after suffering defeats on Sunday.
The writing appears to be on the wall for AC Milan coach Massimiliano Allegri as his side suffered a third loss in four games following a 2-1 slip up at Udinese while rock-bottom Siena claimed a shock 2-0 win over Inter at Giuseppe Meazza.
Udinese put their opponents under the cosh with a Mathias Ranegie goal just before half-time, with Stephan El Shaarawy restoring some confidence for the visitors in the second period with a mercurial finish from 25 yards.
But as Cristian Zapata became the first of two Milan players to be dismissed, Kevin Prince-Boateng later walking for two yellow cards, Antonio Di Natale converted from the penalty spot to earn the Zebrette their first three-point haul of the new campaign and cast Allegri's future into serious doubt.
Second-half goals from Simone Vergassola and Francesco Valiani saw Siena claim their first Serie A victory of the season.
Inter have now lost both matches at home this campaign and already find themselves six points behind Juventus, who beat Chievo on Saturday night.
The Old Lady are now the only club in the league to maintain a 100% winning start to the season after Napoli were held to a goalless draw at Catania, who played nearly the entire match against 10 men.
The hosts had defender Pablo Alvarez sent off after only two minutes for a last-man foul on Edinson Cavani at the Stadio Angelo Massimino, but the visitors were unable to find the breakthrough.
Genoa ended Lazio's perfect start to the season thanks to a goal from former Roma striker Marco Borriello at the Stadio Olimpico.
Despite dominating for large spells of the encounter, Lazio were caught on the counter 11 minutes from time as Borriello sent a low shot past Federico Marchetti after latching on to Luca Antonelli's clever through ball.
Sampdoria also dropped their first points of the season following a 1-1 draw at home to Torino.
It was a tale of two penalties at the Stadio Luigi Ferraris with Rolando Bianchi scoring first from the spot for Torino in the 69th minute before Nicola Pozzi replied five minutes from time.
Pescara survived the second-half dismissal of goalkeeper Mattia Perin to hold on for their first point of the season after a 1-1 draw at Bologna.
Alberto Gilardino gave the hosts the lead in the ninth minute, but Juan Quintero's stunning 40th-minute free-kick proved sufficient for promoted Pescara, who had Perin sent off after the interval when he brought down Gilardino in the area.
Bologna failed to capitalise as substitute goalkeeper Ivan Pelizzoli guessed right to save Alessandro Diamanti's spot-kick.
Palermo's struggles continued as they suffered a 1-0 defeat at Atalanta, who were grateful for Cristian Raimondi's 88th-minute strike.