Sprouse began playing David Schwimmer's on-screen son Ben Geller on Friends when he was 7 years old
Aniston, 54, was asked about her former Friends costar during an interview alongside her Murder Mystery 2 castmate Adam Sandler, who also previously worked with Sprouse and his twin brother, Dylan, in 1999's Big Daddy.
"What?" Aniston asked, raising her hands above her head in shock before adding of both Sprouses: "No, no, they're not. Wow, that's so crazy."
Sprouse joined the ensemble comedy in its sixth season, though his last appearance was in the season 8 episode "The One Where Joey Dates Rachel." He shared many on-screen moments with Aniston throughout his time on the series, including in "The One with the Truth About London," which saw the actress's character Rachel Greene teaching Ben pranks.
In the years since the series ended in 2004 after 10 seasons, Cole has opened up about his former crush on Aniston. The Suite Life of Zack and Cody alum even said his attraction made it "quite difficult to work in front of her."
"I was a child. I would stammer a lot, and I would forget my lines," he said on The Drew Barrymore Show in 2021. "I feel like I'd maintain my composure a bit more effectively now, but it was quite difficult when I was a kid."
"I was teased a little bit by the crew, because they saw it," he added. "I would just forget, and be looking at her. But then, the whole world had a crush on Jennifer Aniston."
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All 10 seasons of Friends are now streaming on HBO Max, and Murder Mystery 2 premieres Friday on Netflix.
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