Saturday's domestic spat between the world's two richest clubs is a potential decider in a La Liga title race in which leaders Real hold a four-point lead over Barca with five matches to play.
There is the added possibility of Barca and Real taking their rivalry to an all-Spanish Champions League final, a kind of 'super clasico', in Munich on May 19.
"Our wish is that the Champions League final is between Real Madrid and Barcelona," Spain coach Vicente del Bosque said on Monday, brushing away suggestions that the bitter rivalry would upset national team unity ahead of Euro 2012.
"We need to enjoy this moment which is difficult to repeat for Spanish football, where five of the eight semi-finalists (in European club competitions) are from our league."
Athletic Bilbao take on Portugal's Sporting, and Atletico Madrid play Valencia in the Europa League semis which start on Thursday.
Valencia lie third in La Liga but are a massive 29 points adrift of second-placed Barca, and 33 short of leaders Real, the top two having left everyone behind with a relentless pace.
Jose Mourinho's and Pep Guardiola's sides have only suffered two defeats each, and are re-writing the goalscoring record books as they bid to outdo each other.
Mourinho, in his second season at the Bernabeu, is closing on the club's first league title in four years and his team have equalled the league's goal-scoring record of 107 set by the Real side managed by John Toshack in the 1989-90 campaign.
Toshack's side were led by somersaulting Mexican striker Hugo Sanchez, who equalled the league scoring record set by Telmo Zarra of 38 goals.
Mourinho's team arguably may not be as fluid as that of Emilio Butragueno and company, but in Cristiano Ronaldo they have their own goal-scoring machine.
The Portuguese forward has already broken the league record he set last season of 40 and the firepower of strikers Ronaldo, Gonzalo Higuain and Karim Benzema is Real's main weapon.
"Now Real Madrid have to navigate stormy waters," honorary Real president Alfredo Di Stefano said in sports daily Marca on Monday.
"We need to get round a tight last bend and it is goals that will bring us happiness."
The Spanish and European champions have steadily reeled in Real over the last month, led by the in-form Lionel Messi who has matched Ronaldo's 41 league goals and amassed a whopping 63 in all competitions.
The Argentine World Player of the Year is four goals away from the all-time record of 67 set by former Bayern Munich striker Gerd Mueller in the 1972-73 season.
Barca, who have only lost once in 10 matches against Mourinho's Real, have an outside chance of a fourth consecutive league title and of becoming the first side to retain a Champions League crown. (Reporting by Mark Elkington, editing by Justin Palmer)