Former Juventus striker Fabrizio Miccoli put Palermo in front seven minutes in with a shot under the legs of Italy goalkeeper Gianluigi Buffon, then Giulio Migliaccio doubled the lead in the 20th minute with a header off a corner.
Juventus thought they should have had a penalty after a handball by Palermo defender Cesare Bovo in the 34th minute, but the referee waived the Juve appeals off, Juventus midfielder Claudio Marchisio pulled a goal back for Juve in the 36th minute, but they were never able to get that second goal and a share of the points.
Elsewhere Wednesday, Roma was held to a 1-1 home draw by Brescia, which equalized in the 69th through Brazilian striker Eder after Marco Borriello had put Roma ahead. Udinese drew 1-1 with Bologna, while Cesena and Catania also ended up 1-1. all square.
AC Milan, which drew 0-0 with Lazio on Wednesday, now holds a five-point lead over Napoli, with Lazio seven points back and Roma nine points behind in fourth. Five-time defending champion Inter Milan, which has played two fewer matches, is 10 points back entering its game at Bari on Thursday.