Ahead of the rest of the weekend fixtures, Rafael Benitez's side have a one-point lead on Roma and a three-point advantage on Inter Milan and Juventus.
Juventus face Torino away in the city derby in today's early match where Antonio Conte's men would have to win and score several goals if they are to take command of the league.
Inter face Cagliari away in one of five afternoon's games while Roma, who began the weekend top of the table with a two-point lead on their rivals, host Bologna in the late game.
But with Benitez resting forwards Marek Hamsik and Gonzalo Higuain ahead of Tuesday's Champions League clash against Arsenal at the Emirates, Pandev made the most of a rare start yesterday.
The Macedonian international opened the scoring in the 14th minute when he pounced on a poor backpass from Slovakian midfielder Juraj Kucka to beat Mattia Perrin with a clinical left-foot strike.
Pandev doubled Napoli's lead barely 10 minutes later when he finished off the good work of fellow forward Lorenzo Insigne.
With Duvan Zapata still short of full match fitness, Benitez replaced the Colombian striker with Higuain in the 59th minute, but the Argentinian international failed to threaten Perrin in the hosts' net.
"It's just a shame we didn't put the game beyond reach earlier with a third goal, we had the opportunities.
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