Real Madrid can bury Atletico's hopes of winning La Liga with a third straight victory against their city neighbours on Sunday that would leave the capital's second club trailing by six points.
Atletico stunned their bitter local rivals 2-1 at Real's own Bernabeu stadium in last season's Copa del Rey final and followed up with a 1-0 success at the same venue in La Liga at the end of September.
However, Real have greatly improved as the season has progressed and they dumped holders Atletico out of this term's cup 5-0 on aggregate in their two-legged semi-final this month.
Unbeaten in 27 matches in all competitions, Real are in ominous form before Sunday's trip across town to Atletico's Calderon stadium and will be buoyed by their 6-1 success at German side Schalke 04 in the Champions League on Wednesday.
They took over from Barcelona, who host promoted Almeria on Sunday, at the top of La Liga last weekend when both Barca and Atletico suffered surprise defeats. Real have 63 points with 13 games left, with Barca, chasing a fifth title in six years, and Atletico on 60.
Real coach Carlo Ancelotti, who took over from Jose Mourinho at the end of last term, has eliminated the defensive lapses that cost his team earlier in the season.
With Cristiano Ronaldo, Karim Benzema and Gareth Bale in a three-pronged attack, the Italian has one of the most lethal forward lines in football and each scored twice in Wednesday's romp in Gelsenkirchen.
"We have a lot of potential up front," midfielder Xabi Alonso, whose composure and passing ability help Real control their opponents, told reporters after the Schalke game.
"We create a lot of chances and it's good news that the three forwards are fired up," added the Spain international.
"Sunday's game is very important for us and it is going to be very tough. We are confident but we know that each match is a different story. If we don't go out with the same focus as today any team is capable of giving us a scare."
Atletico, who are also through to the last 16 of the Champions League, are mounting a genuine challenge for the La Liga title for the first time since they won a league and cup double in 1996.
Diego Simeone, a former Argentina midfielder, was part of that team and has transformed the club since he took over as coach at the end of 2011, leading them to a Europa League triumph in 2012 and the cup success last season.
However, last weekend's shock 3-0 reverse at Osasuna, when Simeone left a number of key players out of his starting lineup, suggested they may not have a deep enough squad to cope with a gruelling calendar.
Fullback Juanfran said the team are keen to put last week's stumble behind them and reignite their title challenge.
"We are keen to prepare the match well and if we beat Madrid things will be different," he said on Atletico's website. "We are playing at our stadium, where we are unbeaten (in La Liga this season) and I am convinced we will play a good match and win," he added.
OPTA MATCH FACTS
Atletico Madrid have not done a league double over Real Madrid since 1950/51, when they went on to become La Liga champions.
The Whites have won their last six trips to the Calderon in La Liga; their best ever run there.
The Red-and-Whites have not won a home derby with Real Madrid since 1999, when they won 3-1.
Real Madrid have scored inside 15 minutes in nine of their last 11 visits to the Vicente Calderon in La Liga.
Atletico have won more league games on a Sunday than any other side this season (nine) while Real are the only unbeaten side on this day.
Real Madrid have scored as many goals in their last three league games at the Calderon (eight) as Atletico have in all 11 derbies played there since promotion.
Diego Lopez has lost four of his last five league games against Atleti.
Atletico Madrid have won all 11 home league games this season in which Diego Costa has scored (15 goals in total for the striker).
Against no other side in his career has Cristiano Ronaldo scored more penalties than he has against Atletico Madrid (five).
Real Madrid have conceded the fewest goals (three) and shots (48) in the second round of fixtures so far; Atleti still have the best record in both across the whole season (19 and 224).
Atletico Madrid are the only unbeaten home side remaining in La Liga; Real Madrid have won the most away games (nine).
The Whites have won 41 of the 45 points available since Xabi Alonso returned to the team; eight more than any other team in this period (Atletico with 33).
David Villa could become the first player to score against Real with four different sides in La Liga in the 21st century.
Real Madrid have scored a league-high 16 goals from outside the box this term; Atletico, a joint-low one.
Raul Garcia and Cristiano Ronaldo are the joint-top scorers in Madrid derbies this season with four goals apiece.
EUROPEAN GAMES COVERED LIVE ON SITE THIS WEEKEND