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She was born in Queens, New York. She attended high school at the High School of Performing Arts and attended college at Syracuse University before dropping out after three years. In 1988, she was an ensemble cast member in the Off-Broadway play Noo Yawk Tawk, providing improvisational comedy.
She joined the sketch comedy series Mad TV as one of its original cast members, remaining on the show for eight seasons, being one of the longest-serving cast members and was also the last remaining original cast member to leave the show. Some of her most popular impressions on the show included Oprah Winfrey and Whitney Houston. She left in 2003 after the eighth season. She also appeared in Sierra Mist commercials with fellow Mad TV cast member Nicole Sullivan and Michael Ian Black.
She has also served as a commentator on E! specials, and served as a co-host on TV Watercooler in 2006. More recently, Wilson has focused on a voiceover career, providing the voices of Principal Davis in The Oblongs, Eva Perón and Harriet Tubman in Clone High, performing her Whitney Houston impression on American Dad!, Debbie in Over the Hedge, Ellie in the video game Ice Age 2: The Meltdown, Iana in Hoodwinked Too! Hood vs. Evil, Streaky in the short Super Pets, Tammy in All Hail King Julien, Nasty Cat in Pig Goat Banana Goat, among other cartoons.
- "Dodge This" - Council Woman, Thunder Girl 1, Blonde Girl
Wilson serves as a mentor for Create Now!, a program that uses art to help troubled children. She has two sisters, named Lysette and Nikki. She and her husband, Cliff Skelton, are currently separated.