A devilishly entertaining encounter had a seemingly impossible number of twists, with Gonzalo Higuain's missed penalty at 2-2 the watershed moment as both teams finished with 10.
The Romans worked effectively on the counterattack in the opening period, when strikes from Marco Parolo and Antonio Candreva gave them an apparently decisive lead.
But Gonzalo Higuain’s tap-in shortly after the break dramatically altered the course of the fixture. After Parolo was dismissed for a second booking, the ex-Real Madrid forward finished clinically once more.
The drama was not done as the Argentine missed a penalty after Faouzi Ghoulam’s red card ensured both teams would finish with 10, and with five minutes left substitute Ogenyi Onazi pinched all three points for the guests. In stoppage time Miroslav Klose headed a fourth.
Napoli, being led by Rafael Benitez for the final time, came into this match aware it needed a victory to leapfrog its opponents into third, but though it dominated possession and territory the club was largely lacking in menace.
The home side did fashion one glorious opportunity when smart combination play from Marek Hamsik and Dries Mertens saw Jose Callejon enjoy the freedom of the Lazio box. However, the Spaniard dallied to check he was onside and dragged the chance wide.
Parolo’s thumping long-range shot gave Lazio the lead, though it took the aid of a slight deflection and some questionable goalkeeping from Mariano Andujar to do so.
Shortly before the break, the home side was caught open after a Kalidou Koulibaly pass was intercepted by Senad Lulic. The Bosman released Candreva, who finished where Callejon had failed earlier at the other end.
The second half started amidst a subdued atmosphere and it was only when Higuain showed his predatory skills by tapping home a Callejon cross that the match was truly ignited.
Napoli enjoyed a barnstorming period in which Mertens had a shot spectacularly cleared from the line by Stefan de Vrij and Callejon saw Federico Marchetti beat away his powerful effort.
Once Parolo was dismissed, the resistance of the guests was broken again when Higuain wrestled a shot inside the near post after bright work down the left from Koulibaly and Mertens.
At that point the momentum in favor of the home side seemed irresistible, yet it was checked when Faouzi Ghoulam was sent off for seeing yellow for a second time.
Benitez’s side continued to push forward and was awarded a penalty when Lulic was adjudged to have felled Christian Maggio. Higuain, however, clattered the resultant spot kick hopelessly high.
Lazio barely had a sniff in the second period, yet substitute Onazi scored literally seconds after coming on before Klose headed a fourth in stoppage time to ensure there was no fairy tale ending for the apparently Real Madrid-bound Benitez.