Inter Milan crashed to their first defeat of the Serie A season on Wednesday, going down 2-1 at home to Sassuolo.
Inter went into the game with a perfect record of five wins in five and looked in control at 1-0 ahead thanks to a Denzel Dumfries goal on the stroke of half-time at the San Siro.
Sassuolo levelled in the 54th minute when Nedim Bajrami scored with a long-range effort which caught out goalkeeper Yann Sommer.
Domenico Berardi hit the winner 10 minutes later as Sassuolo claimed all three points to follow up last week's win over Juventus.
Inter remain top of the table on goal difference ahead of AC Milan who earlier defeated Cagliari 3-1.
"After a good first period where we should have scored more than one goal, but we lost our focus especially after the equaliser," said Inter coach Simone Inzaghi.
"Losing in front of our home crowd hurts us, we have to understand what happened, even if the schedule, with our next match on Saturday, doesn't really give us time to take a step back."
After a defeat and two draws, champions Napoli returned to winning ways with Victor Osimhen playing a starring role.
The Nigerian striker scored his fourth goal of the season after 39 minutes with Khvicha Kvaratskhelia ending a long goal drought by finding the net in the second half.
Osimhen, top scorer in Serie A last season, had cut a controversial figure at the weekend when he showed his displeasure at being taken off by coach Rudy Garcia in the 0-0 draw with Bologna.
On Tuesday, his agent threatened Napoli with legal action for having published a video on the club's TikTok account, since deleted, mocking the striker for missing a penalty in that game.
Napoli are now fifth in the table with 11 points, four points behind the two Milan clubs.
"The Napoli from last season may be back," said Kvaratskhelia.
- Pioli's 200th win -
AC Milan fought back from a goal down to defeat Cagliari.
Milan were without injured goalkeeper Mike Maignan as well as strikers Olivier Giroud and Rafael Leao.
Cagliari, searching for a first win of the campaign, grabbed a shock 29th-minute lead through Angolan winger Zito Luvumbo who capitalised on a mix-up in the Milan defence to shoot past Marco Sportiello.
Milan, however, hit back with Noah Okafor levelling in the 40th minute when he beat goalkeeper Boris Radunovic from a cross by Christian Pulisic.
In first-half injury-time, Fikayo Tomori added Milan's second thanks to the work of Yacine Adli who was starting a game for only the second time since his arrival at the club in July 2022.
Stefano Pioli's side made sure of the three points on the hour mark when Ruben Loftus-Cheek hit the target.
The win was a fifth in six matches for AC Milan who are level on 15 points with Inter.
"We deserved our victory in a match which was not a formality," said Pioli who celebrated his 200th win as a coach in Serie A.
However, he admitted there had been "naivety" over the goal Milan conceded.
"We know that it is the matches against our direct rivals for the title which will impact our place in the table, but these matches which, on paper, seem simple will be very important at the end of the season," he added.
Empoli, who sacked coach Paolo Zanetti last week after a 7-0 thrashing at the hands of Roma, celebrated their first win of the season.
Tommaso Baldanzi scored the only goal in a 1-0 win over Salernitana.
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