Antonio Di Natale scored a hat-trick as Udinese recorded an impressive win which denied Napoli a place in the top three in Serie A.
Marek Hamsik replied for the visitors but also missed a penalty as the Partenopei suffered only their second defeat on the road this season.
Udinese, however, remain unbeaten at the Friuli stadium since mid-September and now sit just four points behind their opponents.
Di Natale saw his first glimpse of goal after 10 minutes, trying his luck from 30 yards only to see his effort saved by visiting goalkeeper Morgan De Sanctis.
But the hosts were ahead six minutes later through a Di Natale penalty. De Sanctis brought down Alexis Sanchez with a clumsy challenge and the captain made no mistake from the resulting spot-kick.
Sanchez then fired wide as Udinese immediately set about adding to their lead, while Di Natale volleyed over the bar with 38 minutes on the clock.
But the striker found himself on the scoresheet again on the stroke of half-time with a superb curling effort from 30 yards which nestled in the top right corner.
Napoli's first real chance of the match arrived seven minutes after the restart when Hamsik was unfortunate to see his shot skim the right post with home goalkeeper Samir Handanovic well beaten.
But they conceded a third goal after 57 minutes when Hamsik let a corner from Di Natale slip through his legs and in at the near post.
Hamsik made some amends for his error two minutes later, finding the bottom right corner with a drilled shot from distance.
And a Napoli fightback looked on the cards when Edison Cavani won his side a 66th-minute penalty following a foul from Maurizio Domizzi.
But Hamsik failed to add to his personal tally with Handanovic making a great save to deny the Slovakian.
Cavani, the joint leading scorer in the league alongside Inter Milan's Samuel Eto'o, wasted a good opportunity to boost his figures when he headed Hamsik's cross wide.
The Uruguay international then put a diving header wide of an open net from close range as Napoli resigned themselves to defeat.