Bayern could be knocked from top spot even before kick-off if second-placed RB Leipzig pick up a point at Bayer Leverkusen on Friday night to extend their unbeaten record to 11 matches.
But all eyes will be on Dortmund, where the German league's top two strikers -- Borussia's Pierre-Emerick Aubameyang and Bayern's Robert Lewandowski -- will go head-to-head.
Fifth-placed Dortmund are six points behind Bayern in what promises to be a battle royal and between them, Aubameyang and Lewandowski have scored 18 league goals.
"It's not just the fans who look forward to this game, but the players as well," said Bayern's Germany forward Thomas Mueller.
"It's the best game of the year, because it's the hardest to win.
"It's the biggest challenge."
The battle of Germany's top two teams has been dubbed 'Der Klassiker' by the German media in recent years, but Dortmund's last league win over Bayern -- home or away -- was more than two years ago.
Nevertheless, hosts Dortmund are eager for their first win over the Bavarians at Signal Iduna Park since April 2012.
Both sides have stars with a point to prove against their former club.
Bayern's Germany defender Mats Hummels can expect to face a cacophony of whistles and jeers every time the ex-Dortmund captain touches the ball.
"If we lose then lots of teams, including Dortmund, will be very close behind us (in the table)," said Hummels.
Mario Goetze, who spent the last three seasons in Munich, will lead Dortmund's attack while defensive midfielder Sebastian Rode is hoping for a start against ex-club Bayern.
Dortmund winger Marco Reus could make his first start of the season after a groin injury while Bayern have had both defender Jerome Boateng and winger Franck Ribery back in training after knocks.
Dutch winger Arjen Robben has been given the all clear after complaining of a sore thigh in the Netherlands' 3-1 win over Luxembourg on Sunday in a World Cup qualifier.
But Bayern are waiting to hear if Arturo Vidal is fit after the Chile midfielder played in a mid-week World Cup qualifier while carrying an injury -- despite requests not to do so from Bayern's chairman Karl-Heinz Rummenigge.
"Best not to ask," Vidal told reporters after hurting his thigh during Chile's 3-1 win over Uruguay, having also returned from international duty in October with an ankle injury.
Elsewhere, third-placed Hoffenheim, under Julian Nagelsmann, the youngest coach in Bundesliga history at 29, are at home to bottom side Hamburg on Sunday.
Hoffenheim are unbeaten this season and have caused opponents all manner of problems with a solid 3-5-2 formation. They held Bayern to a 1-1 draw last time out while Hamburg have yet to win a game this season.
Borussia Moenchengladbach have failed to win any of their last five games and they face Cologne on Saturday in the Rhineland derby.
Coach Andre Schubert is under pressure and his side needs a confidence-boosting win for next Wednesday's Champions League clash at home to Manchester City with Gladbach clinging on to third place in Group C.
Fixtures (kick-offs 1430 GMT unless stated)
Bayer Leverkusen v RB Leipzig (1930)
Borussia Moenchengladbach v Cologne, Mainz v Freiburg, VfL Wolfsburg v Schalke 04, Augsburg v Hertha Berlin, Darmstadt v Ingolstadt, Borussia Dortmund v Bayern Munich (1730)
Hoffenheim v Hamburg, Werder Bremen v Eintracht Frankfurt (1630)