Internazionale suffered their first league defeat of the season as they were stunned 1-0 by Napoli.
Elsewhere, Fiorentina boosted their UEFA Champions League hopes with a last-gasp win at Juventus, while bottom club Cagliari picked up a vital three points.
Livorno climbed out of the bottom three in Serie A with a slender home win, which dumped opponents Catania into the relegation zone.
With their crucial UEFA Champions League clash against Liverpool not for another nine days, Internazionale could afford to focus fully on extending their six-point lead at the top of Serie A.
However, they were caught napping as Marcelo Zalayeta struck for Napoli in only the third minute.
Inter were then frustrated for the remaining 87 minutes as Napoli held on for a famous victory.
Third-placed Juventus conceded two late goals to slip to a 3-2 home defeat to fourth-placed Fiorentina, whose match-winner was also sent off.
Massimo Gobbi put the Viola ahead on 19 minutes before former Liverpool midfielder Mohamed Sissoko equalised just before the half-hour mark.
Italy international Mauro Camoranesi gave Juve the lead on 57 minutes only for substitute Papa Waigo to bring Fiorentina level 15 minutes from time.
Fellow substitute Pablo Osvaldo grabbed the winner three minutes into stoppage-time, only to collect a second yellow card for his celebration.
Cagliari came from behind to win 2-1 at home to Genoa to inject some much-needed impetus into their battle to avoid the drop.
Genoa were in front on 14 minutes through Alessandro Lucarelli, but Robert Acquafresca's brace before half-time secured the points for Cagliari.
A 62nd minute goal from half-time substitute Alessandro Diamanti earned Livorno an important 1-0 home success over fellow strugglers Catania.
Antonio Cassano scored and was sent off as Sampdoria twice came from behind to draw 2-2 at home to Torino.
Gianluca Comotto put the visitors ahead on 17 minutes before Luigi Sala equalised in first-half injury-time.
David Di Michele's penalty six minutes after the break restored Torino's lead, only for Cassano to level on 53 minutes before the on-loan forward was dismissed three minutes from time.
Udinese consolidated their position in fifth spot after a 2-0 win at home to Atalanta.
Fabio Quagliarella opened the scoring after 29 minutes and two minutes later Antonio Di Natale made the game safe.
Siena eased their relegation fears with a 2-0 win at Empoli, who finished the game with 10 men.
Daniele Portanova scored after 33 minutes before Siena substitute Christian Rigano added the second four minutes into stoppage-time, while Empoli had Davide Moro sent off.
Reggina are now just one point off the foot of the table after a 0-0 draw at home to Palermo.