The New York Times said Specter died of complications from non-Hodgkins lymphoma.
Specter was first elected to serve Pennsylvania in the U.S. Senate in 1980 and served five consecutive terms. A longtime moderate Republican, he started his political career in the 1960s as a Democrat and switched back to the Democratic Party in 2009. He was defeated in the Democratic primary in 2010.
Specter served for 30 years on the Senate Judiciary Committee beginning in 1981, including as chairman from 2005 to 2007, and participated in the confirmation hearings of 14 U.S. Supreme Court nominees, according to his biography on the University of Pennsylvania Law School website, where he served as an adjunct faculty member.
In addition to his work on the Judiciary Committee and other committee appointments, Specter was chairman of the Senate Select Committee on Intelligence from 1995 to 1997, and has served as a senior member of the Senate Appropriations Committee.
Before his election to the U.S. Senate, Specter served as assistant district attorney and as district attorney of Philadelphia. From 1963 to 1964, Specter was assistant counsel to the Warren Commission investigating the assassination of President John F. Kennedy, where he originated the theory of a single-bullet fired by a lone gunman.
Specter, a native of Wichita, Kan., served as a second lieutenant in the U.S. Air Force Office of Special Investigations during the Korean War.
Specter was diagnosed with stage IVB Hodgkin's disease in 2005 but continued working full-time in the Senate. He wrote a book about the experience, "Never Give In: Battling Cancer in the Senate." Specter underwent treatment for brain tumors in 1993 and 1996. He also had heart bypass surgery in 1998.
"Arlen Specter was always a fighter," President Barack Obama said Sunday in a statement.
"From his days stamping out corruption as a prosecutor in Philadelphia to his three decades of service in the Senate, Arlen was fiercely independent -- never putting party or ideology ahead of the people he was chosen to serve. He brought that same toughness and determination to his personal struggles, using his own story to inspire others."
Specter earned his bachelor's degree in International Relations from the University of Pennsylvania in 1951, and his law degree from Yale University in 1956.