Rafael Benitez's side lost ground on Juventus and Roma as it was forced to settle for a draw against the Grifone.
Napoli was denied victory on Monday as Genoa loanee Emanuele Calaio scored a sensational goal against his parent club to secure a 1-1 draw.
Gonzalo Higuain's 18th minute strike looked set to prove decisive for Rafael Benitez's side, which sits third in Serie A.
However, substitute Calaio provided a stunning twist to an entertaining match with seven minutes remaining, beating Pepe Reina with a curling free kick from 30 yards.
Calaio was understandably restrained in celebration after his wonderful left-footed strike punished the hosts for not putting the game to bed.
Napoli now sits six points behind second-placed Roma having played a game more, while Genoa remains 11th.
After Higuain had fired wide on the turn early, the lively Dries Mertens twice looked to find the top-right corner, narrowly missing the target with his second attempt after Mattia Perin had saved his initial effort.
The hosts' early dominance was rewarded when Higuain latched on to a perfectly weighted through ball from Marek Hamsik before lifting the ball over Perin to take his Serie A tally this season to 13 goals.
Genoa responded well, with Luca Antonelli heading over from a free kick and Moussa Konate seeing a goalbound shot cleared by Federico Fernandez with Reina beaten.
Higuain then sent a driven strike just past Perin's right-hand post before Matuzalem escaped with just a yellow card after appearing to jump into a challenge with Fernandez.
There were further chances at either end before the interval, Mertens threatening for Napoli on two further occasions either side of Konate seeing a free header saved by Reina.
Konate dribbled into a promising position three minutes into the second half, but was unable to capitalize as Fernandez got back to make a crucial intervention.
A similarly fine challenge from Luca Antonini shut out Napoli's Jose Callejon before Genoa saw another opportunity go begging through Giuseppe Sculli, who was unable to hit the target after good work from Konate.
Sculli also brought a save from Reina with Benitez's side looking vulnerable, yet it was Calaio who had the final say.