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Picchiotti has been active in the dance music scene for over 20 years, establishing his reputation as a house, electronica and pop music DJ at Chicago clubs such as Shelter and Crobar. He has remixed songs by a wide array of performers such as Madonna ("Bedtime Story"), t.A.T.u. ("All The Things She Said"), Paula Abdul ("My Love Is for Real"), LaTour ("People Are Still Having Sex"), Lisa Stansfield ("Never, Never Gonna Give You Up"), S Club 7 ("Two in a Million") and more recently, Rihanna ("Rockstar 101") and Liza Fox ("Gimme All (Ring My Bell)"), among many others.
In the early 2000s, Picchiotti collaborated with pop superstar Kylie Minogue on two tracks: "Butterfly" and "Give It to Me". "Butterfly" originally appeared on Minogue's 2000 album, Light Years, then appeared as a bonus track on her multi-platinum 2002 album, Fever. Picchiotti produced this track and later remixed it. "Give It to Me" appeared on Minogue's Fever album and was co-written and produced by Picchiotti.
He scored his first #1 single on the Billboard Hot Dance Club Play chart as a featured artist in July 2008, with the song, "Turn It Up", which was credited to 'Mark Picchiotti presents Basstoy'. The vocals on "Turn It Up" are performed by Dana Devine. In 2002 he released Runnin' which reached number 13.