The Dutch legend has spoken of how the Spanish rival clubs are ahead of all their rivals, while also speaking in support of Tito Vilanova
The teams meet on December 10, with Madrid currently three points clear of their Catalan rivals at the top of La Liga.
The two clubs last met in August when Barcelona were 5-4 aggregate winners in the Spanish Supercopa, and Cruyff was unable to choose a favourite for next month's meeting.
"The outcome is unknown. What we do know is that the two teams are the best in Europe," the Dutchman told Mundo Deportivo.
Cruyff was then keen to show support towards Barcelona's assistant coach Tito Vilanova, who has recently undergone surgery to remove a tumour from his parotid gland.
"The advantage he has is that he is physically very strong. He is recovering, this is an important detail. He has the support of many around him because he is a nice guy," he added.
Barcelona return to Liga action on Saturday evening, when they visit Getafe.
Starting last week and continuing every Friday through to January, Goal.com will publish extracts from Graham Hunter's highly-anticipated book, Barca: The Making of the Greatest Team in the World. Friday's second extract was about how Joan Laporta and Sandro Rosell used David Beckham as a vote-winner in the club elections of 2003, even though a deal was already done between Manchester United and Real Madrid.