The world's most expensive player has won over the Bernabeu faithful with some breathtaking performances and will have the perfect opportunity to showcase his talents against the Premier League leaders.
The managerial battle between Real's Jose Mourinho and United's Sir Alex Ferguson is another fascinating aspect of the tie but Ronaldo's bid to destroy his old team mates should take centre stage as two of the world's biggest clubs lock horns.
It is a significant turnaround from a difficult patch earlier in the season when he raised eyebrows and prompted talk of an exit from the club by telling reporters he was unhappy "for professional reasons".
"The Champions League is very special at Madrid because we want to win a 10th European title," Ronaldo said in an interview with British daily The Sun. "For me it is the pinnacle.
"There are so many memorable matches that remain in the minds of the players and the fans. I want to make my contribution, I want to leave my mark."
At Real he has netted 182 in 179 matches, a far higher goals-per-game ratio than Di Stefano's 308 in 396 appearances in the 1950s and 60s when he helped the club to five successive European titles.
Wednesday's match also renews the intriguing rivalry between Mourinho and Ferguson who have struck up a friendship over the years and are known to enjoy a glass of wine together.
"I feel privileged to be his friend because he is one of the most important people in the football world and, much more importantly, because he is a good person," Mourinho said after watching United beat Everton 2-0 at Old Trafford on Sunday.
"Madrid-United is the match that everyone wants to see. The world won't be watching any other Champions League games so I hope we can give the world what they expect."
Mourinho has faced United twice at this stage of the Champions League, starting with Porto's success on the way to winning the trophy in 2004.
