Los Blancos go into the game on top of the table and will take enormous confidence out of the fact that it's been 12 years since their city rivals last beat them.
However, Jose Mourinho's side have seen their lead over Barcelona cut to just one point and Schuster concedes that Madrid cannot take anything for granted against the Rojiblancos, who are chasing a Champions League place.
"Anything can happen in a derby," the former Madrid and Atletico attacking midfielder told Radio Marca. "They can have goals and dismissals. The derbies are special.
"There is no doubt Madrid are favourites, but this is a key moment in their season. Atletico also need points to get into contention for a European place."
Schuster is also of the opinion that even if Madrid do pick up three points at the Vicente Calderon, they will still have plenty of work to do if they are to land the title.
"I do not think Madrid will be champions if they win the derby," he argued. "There is still another Clasico and other games against opponents who are fighting for their lives."
Madrid's meeting with seventh-placed Atletico gets underway at 22.00CET.
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