The four-time Ballon d'Or winner is believed to be keen to leave Madrid this summer due to allegations from the Spanish tax authorities that he defrauded them of €14.8m (£12.9m).
Calderon was at Real when the club bought Ronaldo from the Red Devils in a then-world record £80m deal in 2009.
"It would be a big mistake if [current president] Florentino Perez doesn't try to keep him with us," Calderon told talkSPORT.
"He has broken all the records at the club, he has got three Champions Leagues in four years and La Liga this year. He has been a very important player. It took me a long time and a big effort to sign him when Man United didn't want to let him go. We have to keep him.
"I think he will stay. I hope so. It would be very bad business to sell him. It doesn't matter what we can get for him. There is no replacement for him. I don't see anybody in world football who can substitute for him. I hope and wish he can stay with us until he retires."
Ronaldo has scored 406 goals in 394 appearances for the Spanish club.