Many comedians wield sharp tongues. Hers is downright serrated. Few can skewer both themselves and global superstars in one sentence: “I’m at least as feminine as Tom Cruise.”

Practicing her specialty, she targets a well-known comedy roast victim: “Would Baywatch have been No. 1 if it were Jimmy Kimmel’s boobs jiggling in slow motion?”

Ha!—and youch! Both can apply when Lisa Lampanelli grabs the mic. “Every interview, someone says to me, ‘They call you the Queen of Mean.’ Who calls me that? Me!” she says with genuine delight. “I love that not a lot of people can do it. It’s a badge of honor.”

Insult humor—godfathered by her idol, Don Rickles—is comedy bomb-throwing, and Lampanelli is a topflight practitioner in a genre for which the key, she says, is to be the least prejudiced person in the room. “If I’m cut off in traffic, I’m not going to go, ‘You dirty … whatever.’ I’m going to go, ‘Hey …’ ” Whoa, whoa, whoa!—let’s just call it a colorful word for a specific element of the rear anatomy. “You have to think there is no group that is less than the other. If you can look at yourself in the mirror and know you’re not coming from an evil place, you’re fine.”

The Queen of Mean (hey, she said it, OK?) says some fans go to extra lengths to ensure getting in her line of verbal fire. “I get lots of tweets before shows,” Lampanelli says. “People name their seat number and say, ‘Please make fun of me, I’m the guy who will be wearing this.’ It’s a unique psychology. It’s like when you’re asked to go onstage and help a magician, like ‘I’m included, I’m a part of this.’”

To Donald Trump: “You’ve put up more worthless hotels than an autistic kid playing Monopoly.”

About Larry the Cable Guy: “He’s Mr. T without the acting chops.”

Yet when comic grenades are lobbed back at her, she is … just fine with it. Say, when Seth McFarlane noted both Pamela Anderson and Lampanelli at a David Hasselhoff roast, cracking that “the most and least downloaded women on the Internet” were in the same room. Ooooh … “I love it when people are roasting me and it’s funny,” says Lampanelli, who grew up a devotee of the old Dean Martin celebrity roasts. “When it’s a cheap shot that’s stupid and not funny, it’s more of, ‘Put some effort in when you’re making fun of me. I put in effort when I’m making fun of you, you …’” (Whoops—insert that rear anatomical reference again.)

Lampanelli found serenity in an attitude shift she attributes to spirituality she discovered while caring for her dying dad. “I felt this big lack of doing service, so I switched my attitude,” she says. “When I do a show now, I’m here to give laughs, not get laughs. It’s about them, not Lisa and her fame and money. It shifted how I felt about myself. My dad put that in my life just seeing how he was so great and nice to people up until the end. And it helped me write my play that will be seen by women who have food and body issues and it will serve them.”

That play by Lampanelli—who famously shed 100 pounds—is Stuffed, set to debut off-Broadway Sept. 23. Until then, there are comic flamethrowers to launch.

“I was sweating like Kathy Lee at a Carrot Top look-alike contest.”

“Betty White is so old that on her first game show ever, the grand prize was fire.”

Ha!—and youch!

The Palazzo, 9:30 p.m. July 30, starting at $49.50 plus tax and fee, 16+ with adult. 702.414.9000