Serie A champions Juventus pulled ahead of the rest of the pack with a 2-0 win over Chievo as their closest challengers slipped up on a dramatic fourth round of matches Sunday.
Lazio joined a host of other teams who had slipped up earlier in the day when they suffered their first league defeat of the season as Marco Boriello gave a gutsy Genoa side a 1-0 win at the Olympic Stadium.
Juventus, who won the league ahead of AC Milan last season, are now the only team to have a 100 percent record.
Earlier, Napoli's three-match winning run came to an end when they were held at Catania, a fate also suffered by Sampdoria who were held to a 1-1 home draw by Torino.
Juventus's bid to defend their title was also reinforced after both Milan clubs suffered defeat on Sunday.
Inter remained in sixth place but are now six points off the pace after a stunning 2-0 defeat at the San Siro to bottom of the table Siena.
Simone Vergassola silenced the home fans with a 73rd minute opener and Francesco Valiani came off the bench to inflict further damage with a goal on the stroke of full-time.
Inter's second defeat at home, following a 3-1 reverse to Roma, is likely to prompt suggestions there is a curse at the San Siro: so far this season, neither Inter nor AC Milan have won there.
Despite losing to the league's least successful side, Inter coach Andrea Stramaccioni did not seem unduly concerned.
"It's a bad defeat for us and it stings," Stramaccioni told Sky Sport Italia.
"But we can't let a defeat get in the way of the ambitions of a new team that is still looking for consistency."
By far the biggest shock of the weekend was Milan's 2-1 away defeat to Udinese, a third league reverse which leaves the seven-times European champions in lowly 15th place.
Despite Italy under-21 international Stephan El Sharaway levelling Swedish striker Mathias Ranegie's 40th minute opener 10 minutes after the restart, the visitors endured a catastrophic end to the match.
Milan's Colombian defender Cristian Zapata was sent off, allowing Antonio Di Natale to score Udinese's second from the spot.
The visitors' hopes of levelling suffered a blow seven minutes from time when they were reduced to nine players after Kevin Prince Boateng was red-carded.
Milan coach Massimiliano Allegri was defiant post-match, telling Sky Sport Italia: "It wouldn't make sense to talk of my dismissal as it's not my decision."
He was later given the backing of club CEO Adriano Galliani, who believe the team showed a marked improvement.
"Allegri has my confidence and that of (club) president (Silvio) Berlusconi," said Galliani. "Milan played far better, I saw a team improvement."
On Saturday Juventus claimed their fourth straight win thanks to Champions League hero Fabio Quagliarella's brace. Quagliarella had come off the bench to score the equaliser for Juve in their 2-2 draw at Chelsea on Wednesday.
And the big striker put in a brilliant all-round performance with two goals in the space of five second-half minutes.
The former Napoli striker said he wanted to show the club he is ready to start as a regular.
"This has been one of the greatest weeks of my life. Today I wanted to show that I'm ready and I think I did that," Quagliarella told Sky Sport Italia after the game.
"It was great to be given a standing ovation from the fans. It shows they appreciate that I've done my job."
The Cagliari v Roma match was controversially postponed hours before kick-off after the Sardinian club's president invited fans to the match despite an official decision for it to be played in an empty stadium.