TVGuide.com quoted writer-producer Eileen Heisler as saying Romano is in talks to guest star in the show's one-hour Season 3 premiere.
Heaton and Neil Flynn play Frankie and Mike, a Midwestern couple struggling to make ends meet while raising three children, in "The Middle."
Romano and Heaton previously starred together on the classic comedy series "Everybody Loves Raymond," which ran for nine seasons from 1996 to 2005.
"It's looking promising," Heisler said of a Romano-Heaton reunion. "Someone from Frankie and Mike's past we'd see in flashback interfering with their honeymoon."
"If you have Ray, you want it to be organic and make sense, and this would. I think he'll have a blast!" Heaton told TVGuide.com.
Doris Roberts, who played Romano's character's mother on "Raymond," plays a recurring role as a teacher on "The Middle."