A source tells PEOPLE that the couple, who dated on and off for two years, split recently, and the 38-year-old confirmed her single status while interviewing her friend, actress Mary McCormack, on Chelsea Lately on Tuesday night.
"Let's talk about your single situation," McCormack joked, trying to work out the reason for the comedienne's love trouble. "I'm looking for a pattern. I was thinking about who you dated."
She began listing the men the talk show host had been out with: TV exec Ted Harbert followed by "a buff Canadian animal trainer."
"He threw me around," Handler said with a laugh.
"And then just when you think you know where you stand, you throw in – I call him Curtis – it's Fitty [50 Cent]," McCormack, who stars in the new NBC sitcom Welcome to the Family, went on to say.
"That was fun though," Handler said of the rapper who she briefly dated in 2010.
"So fun," McCormack, 44, admitted. "But now we're into patchwork craziness. It's boyfriend bingo. It doesn't make any sense."
So Handler came up with a solution: "Maybe I'll start dating a bitch," she responded. "That totally would be something I would do, is date a woman."