Udinese ended Inter Milan's unbeaten start to the Serie A season and led them to surrender the top spot after winning 3-1 at San Siro.
The Nerazzurri -- boasting 12 wins and four draws from their opening 16 games -- were a point clear of Napoli and another beyond reigning champions Juventus heading into Saturday's clash.
But Inter failed to heed the lesson they should have learned in midweek when third-tier Pordenone almost pulled off a shock Coppa Italia result in Milan -- the minnows only losing after penalties.
Massimo Oddo's in-form team took the lead through Kevin Lasagna, with Mauro Icardi promptly levelling, and in the second half Udinese won it through Rodrigo De Paul and Antonin Barak.
Napoli defeated Torino 3-1 later in the day to move into the first place, and Juventus can also move past Inter with a win over Bologna on Sunday.
Udinese raced out of the blocks but Inter absorbed the early pressure and threatened first through Antonio Candreva, who headed Ivan Perisic's cross straight at Albano Bizzarri.
Inter came closer to scoring when Perisic clattered a post with a volley, but in the 14th minute Udinese struck the opener.
When Davide Santon lost the ball in his own box, Silvan Widmer stole in to pick out Lasagna for a close-range finish.
The visitors' celebrations were short-lived, though, as Icardi equalised inside a minute to reach 17 goals for the Serie A season.
Candreva's cross was pin-perfect and Inter captain Icardi twisted his body to finish on the volley.
The Nerazzurri ramped up the pressure before the break, with Candreva, Perisic and Marcelo Brozovic all giving Bizzarri food for thought.
In the 40th minute they came closer still to taking the lead as Perisic's effort from the left sent Bizzarri flying across his goalmouth to punch the ball clear.
When play resumed after half-time it was Udinese who took the initiative, Lasagna connecting with De Paul's pass after Milan Skriniar slipped on the turf.
However, Slovenian stopper Samir Handanovic pulled off a stunning save and the tussle continued.
Udinese, after an anxious wait, were soon exulting when a penalty was awarded by the video assistant referee on the hour mark.
Santon was adjudged to have handled the ball when Widmer crossed for Lasagna and following the VAR review, De Paul stuck the spot kick away.
Inter were crestfallen and Udinese almost grabbed their third when De Paul picked out Seko Fofana for a right-footed attempt that fizzed over the crossbar.
The action continued to swing at San Siro and Skriniar soon rose to nod a Candreva assist against the bar before, in the 77th minute, Udinese landed a killing blow to Inter's undefeated status.
It was not a pretty finish from Barak, who was teed up by Jakub Jankto, but it confirmed the outcome.