The actor, who played Doctor Octopus in Spider-Man 2, said that the role should be recast if the villain is to reappear in a future instalment.
"I think parts are like rental cars. They don't really belong to you... When a new franchise gets booted up, they're bound to [recast the role], if they revisit similar villains," Molina told Crave Online.
"I think for instance a different actor is going to play the James Franco role and if they revisit Doctor Octopus and they get another actor, that's as it should be."
Marc Webb is currently working on a sequel to last year's Amazing Spider-Man, with Andrew Garfield and Emma Stone reprising their respective roles of Peter Parker and Gwen Stacy.
Newcomers to the cast include Shailene Woodley as Mary Jane Watson, Jamie Foxx as Electro, Paul Giamatti as Rhino, and Dane DeHaan as Harry Osborn.
Amazing Spider-Man 2 arrives in theatres on May 2, 2014.