The Watch star played a rival newscaster to Ron Burgundy (Will Ferrell) in the 2004 comedy. Mantooth brawled with the Channel 4 news team after they insulted his mother, the "saint" Dorothy Mantooth.
Speaking to Empire, Vaughn revealed that he is likely to return for Adam McKay's comedy sequel.
"The chances are better than not that Wes Mantooth will be there," he said.
Discussing who could play Mantooth's mother Dorothy, Vaughn added: "I don't know if anyone can fill that role, she's such a saint. Angela Lansbury as Dorothy?"
The Anchorman sequel will take place in 1978, picking up with Ron, Brian Fantana, Champ Kind and Brick Tamland as TV broadcasts start to transition into 24-hour news cycles.
Anchorman 2: The Legend Continues is due to arrive in cinemas in 2013.
> 'Anchorman 2' poster: "The legend continues"
> 10 reasons why we love Anchorman
Watch Vince Vaughn in a video clip from the original Anchorman below: