Two clubs with some of the most fervent fans in Germany meet at the Arena AufSchalke with the hosts looking to keep their recent winning streak going by beating Dortmund for a third time in a row.
It would be the first time since the sixties that Schalke would complete such a run.
"There's no other game in Germany which electrifies the masses as much as this one," said Schalke coach Jens Keller.
"Every player knows what is at stake. A derby win means as much to the lads as it does to the fans.
"A derby is like a cup game. These duels always have their own rules."
Schalke have even more reason to savour a victory on Saturday after going down 3-0 at home to Chelsea in midweek.
"Of course we were disappointed after that game," Keller said at a press conference. "Above all because the clear defeat did not reflect how the game went.
"Nevertheless, we've got to put that game behind us and we're now fully focused on the derby, and nothing else."
Dortmund head into the game in confident mood.
Their 2-1 win at Arsenal in midweek boosted their hopes of reaching the knockout stage of the Champions League.
"But this is another game with another atmosphere, and with an even increased importance," said their coach Jurgen Klopp.
"These are the most special games of the season."
The game comes too soon for Sebastian Kehl, who has returned to training after recovering from an ankle injury, while Ilkay Gundogan and Lukasz Piszczek are also back in training.
Keller will hope to be able to count on former Dortmund player Kevin-Prince Boateng, who has been carrying a knee injury, but Klaas-Jan Huntelaar and Marco Hoger are both out, the former until the new year and the latter for the rest of the season.