Sosa hit 545 homers over 13 seasons with the Cubs while becoming one of baseball's biggest stars. But he was traded to the Baltimore Orioles in 2005 after a sour end to his time in Chicago.
Sosa tells Chicago Magazine for a story in its September issue that his "number should be untouchable because of the things that I did for that organization."
Rookie outfielder Tyler Colvin is wearing No. 21 for the Cubs this season.
Sosa finished with 609 homers in 18 years in the majors. He hasn't appeared in a game since 2007.