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Missanelli attended Pennsylvania State University (Penn State), where he played college baseball as a second baseman for the Penn State Nittany Lions. He graduated from Penn State in 1977. He is also a 1986 graduate of the Delaware Law School of Widener University at the same time he was working for the Philadelphia Inquirer
Born and raised in Bristol, Pennsylvania, Missanelli began his career there as a newspaper writer, working at the Philadelphia Inquirer and eventually moved over to radio working on-air at 610 WIP and 93.3 WMMR. In January 2010, he signed a new multi-year deal at ESPN affiliate, 97.5 The Fanatic. He was fired from 610 WIP in January 2003 and began a show with Joe Conklin on WMMR. Missanelli is also a professor at Saint Joseph's University.
Missanelli reportedly said that Philadelphia fans have been unfairly criticized for being violent and hostile. Missanelli has repeatedly battled the unfairly held perceptions of Philadelphia fans, as he himself has written, "Let me assure that when I tear into a guest, like Michael Wilbon or a Skip Bayliss or a Keith Law, it’s for a good reason that has absolutely nothing to do with me personally and everything to do with having the backs of the people, who have had to tread the filthy water of Philly fan perception, fostered by lazy national media nitwits, way too long." 
- "Mike Missanelli". 97.5 The Fanatic. Retrieved 29 January 2011.
- "Mike Missanelli '86". Weidner Law. Retrieved 29 January 2011.
- Rys, Richard (16 June 2008). "Media: The Misadventures of Mikey Miss". Philadelphia Magazine. Retrieved 29 January 2011.
- Philadelphia sports radio fight is on | STAA. Staatalent.com (2010-06-28). Retrieved on 2011-09-29.
- Mike Missanelli and Skip Bayless Have Nasty Exchange On 950 ESPN | NowPublic News Coverage. Nowpublic.com. Retrieved on 2011-09-29.
- Feature: Media: Game On – Philadelphia Magazine. phillymag.com. Retrieved on 2011-09-29.