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Nicola Pozzi bagged a brace to shock Napoli at the San Paolo, but was stretchered off with a potentially serious knee injury.
The pressure was on inconsistent Napoli, who lost at Sampdoria last week, while Empoli were buoyant after their surprise win over Lazio, although they remained in the bottom three. The Tuscans had lost all three previous top flight trips here and missed suspended hero Ighli Vannucchi, while Andrea Cupi, Gennaro Iezzo and Matteo Contini were out for the home side.
Nicola Pozzi had penalty appeals for contact with Paolo Cannavaro waved away, but got on the scoresheet soon after. The Under-21 international ran into the box to blast Sebastian Giovinco's chipped pass on the bounce.
Marek Hamsik's chest and right-foot strike whistled past the post, then Daniele Bassi parried a Maurizio Domizzi free kick into the path of Hamsik, who couldn't make the most of it.
Empoli went so close to doubling their advantage with Giovinco's free kick, but on the counter Ezequiel Lavezzi got down the left for a low cross that Mannini only needed to tap in from six yards. It was the former Brescia player's first goal in a Napoli jersey.
There was an ugly incident as the two teams went down the tunnel, as Marcelo Zalayeta clashed with Felice Piccolo. The referee witnessed it and both players were sent off during the half-time break.
Empoli restored their advantage with another disastrous defensive error. Cannavaro allowed Antonio Busce's ball from the right to go past him, leaving Pozzi to drill on the bounce from eight yards. However, he sustained a knee injury during that move and had to leave the field on a stretcher.
Napoli were reduced to nine men as Domizzi hauled down Giovinco when clear on goal. The foul started outside the box and finished inside, but the referee awarded the free kick from the initial point of contact.
The Tuscans took advantage and extended their lead. Vittorio Tosto spread the play and Busce's angled drive was fingertipped into the path of the unmarked Budel.
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