The village team, who are setting the pace with a squad of relatively unknown professionals, will be toppled from the summit if champions Bayern win at Hamburg SV on Friday.
Hoffenheim, who lead Bayern on goal difference, host Energie Cottbus on Saturday but will be without Vedad Ibisevic, the league's top scorer with 18 goals, for the rest of the season with a ruptured cruciate ligament.
Ibisevic will hope fellow strikers Demba Ba, Chinedu Obasi and Boubacar Sanogo, brought in on loan from Werder Bremen this week, can fill his shoes.
Obasi also misses out against Cottbus due to a thigh injury while midfielder Carlos Eduardo is suspended for two matches after a punch-up with Hamburg's Ivica Olic in a friendly.
Bayern and Hoffenheim have 35 points from 17 games with Hertha Berlin third on 33, ahead of Hamburg on goal difference.
The 5-1 demolition of VfB Stuttgart in the German Cup on Tuesday sent an ominous warning to Bayern's Bundesliga title rivals.
"This was a clear signal to our competitors that we are ready," said coach Juergen Klinsmann after Bayern's emphatic away win took them into the quarter-finals.
"We are fully armed for the next four months and if we continue playing like that it will be extremely hard to beat us."
Bayern had a shaky start to the season but are still in the hunt for a Bundesliga, German Cup and Champions League treble.
Klinsmann's side travel to Hamburg with no major injury concerns and in the knowledge their last league defeat was back in September.
The defence will also be breathing easier knowing dangerous Hamburg striker Olic, who scored a hat-trick in Tuesday's 3-1 German Cup win over 1860 Munich, will not be playing.
Olic, who has already agreed to join Bayern next season, is banned for two matches following the fight with Eduardo.
Hertha host erratic Eintracht Frankfurt on Saturday while fifth-placed Bayer Leverkusen visit Borussia Dortmund, who are sixth.
Stuttgart, yet to lose in the league under new coach Markus Babbel, will try to make amends for their German Cup rout when they host bottom club Borussia Moenchengladbach on Saturday.
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