"Are you three handed," the late-night host asked the Wrinkle In Time star on Thursday's Jimmy Kimmel Live.
"I've been trying to keep that a secret all these years," Winfrey quipped. "I was hoping you could accept me as the three-handed woman that I am."
Kimmel responded, "Obviously, it's brought you great powers."
Winfrey admitted that she didn't notice the photoshop flub until people on social media called attention to it. "I mean, [photographer] Annie Leibovitz sent me an apology," she recalled. "It's OK, Annie. It's alright that I have a third hand."
Winfrey has a simple theory as to how she ended up with three hands in the photo. "I think they were moving people around and I got a third hand," she told Kimmel.
"I was kind of first thrown by it -- it's a humbling thing to have people think that you can run the country, it's a humbling thing," she said. "I'm the kind of person who tries to listen to signs. I think, 'Well, am I supposed to run the country? I don't think so!'"