Milan - Cameroon forward Vincent Aboubakar hit a brace as Ricardo Quaresma-inspired Besiktas ended Napoli's dreams of making Champions League history with a 3-2 win at the San Paolo on Wednesday.
Napoli welcomed the Turkish champions knowing a third consecutive win in Group B, along with a draw between Dinamo Kiev and Benfica, would secure their entry to the last 16 with three games to spare.
It would have set a new competition record, but despite a promising start at the San Paolo, Maurizio Sarri's men were wasteful in front of goal and paid the price for a glaring Jorginho blunder that saw Aboubakar give the visitors a 2-1 lead by the 38th minute.
Napoli struck back when Manolo Gabbiadini, demoted to the bench after an ineffective display in a 3-1 defeat to Roma last weekend, struck the leveller on 69 minutes.
But Napoli failed to capitalise on the few chances that subsequently came their way and paid the ultimate price when Aboubakar headed Quaresma's delivery past Pepe Reina four minutes from the end.
Besiktas' first win in the group kept them in second place to sit just one point behind Napoli, whose next game in the competition is an away trip to the Vodafone Arena in Istanbul next month.
Dries Mertens was handed a rare start in the striker's role and soon vindicated Sarri's decision to leave Gabbiadini on the bench with a series of early chances before finding a way past Fabri on the half hour.
After just three minutes Mertens won a corner when his drive from a tight angle was blocked by a defender.
When Faouzi Ghoulam found Mertens unmarked 12 yards out the Belgian fired over the crossbar.
Besiktas breached the Napoli net after just 12 minutes when Adriano powered his way through the Napoli defence to fire Quaresma's superbly-weighted ball across the face of goal after the Portuguese had been given too much space on the right.
Quaresma narrowly failed to get on the end of Aboubakar's long ball minutes later, while at the other end Mertens mis-hit a great chance from Ghoulam's long ball that forced Fabri to parry at his nar post.
Mertens finished off a on-two with Jose Callejon with a drive that Fabri collected at the second attempt, then glanced a header wide from Insigne's smart delivery.
Mertens finally made good a minute later when he powered past his marker to meet Callejon's perfectly-weighted delivery from the right to sidefoot past Fabri from close range.
Napoli's joy was short-lived, Aboubakar pouncing on an incredibly poor passback by Jorginho to beat Reina for a 38th minute lead.
Wasteful in open play, Napoli were also off target in dead ball situations.
When Fabri fouled Mertens in the area the referee pointed to the spot, but the Besiktas 'keeper recovered to stop Insigne's tame effort four minutes after the restart.
Gabbiadini replaced Insigne on 65 minutes and four minutes later coolly stepped up to show his club-mate how it is done, beating Fabri from the spot after Caner Erkin had fouled Mertens.
Napoli could have wrapped up a great comeback win but Gabbiadini was ruled offside after beating Fabri at the second attempt and Mertens fired a sizzling shot wide of the far post after outfoxing his marker.
The hosts paid the price in the 86th minute when Aboubakar rose at the far post to meet Quaresma's delivery to beat Reina for the second time.