Specter, 82, who has overcome serious illnesses during the past two decades, was diagnosed six weeks ago with the new form of cancer, CNN reported.
His family declined to say what type of cancer Specter had, but a source told CNN he had a "big flare-up" Monday.
The former senator is suffering from a "serious form of cancer," a source close to his office told CNN.
Specter represented Pennsylvania in U.S. Senate from 1980 until 2011, mainly as a moderate Republican. He switched to the Democratic Party in 2009, saying Republicans had moved too far to the right.
After losing in the 2010 Democratic primary, Specter returned to his law practice, taught at the University of Pennsylvania Law School and became a stand-up comedian, performing a set of largely politically themed jokes, Roll Call reported.
Specter was scheduled to perform last week at the Stu Bykofsky Candidates' Comedy Night, a Philadelphia-area charity fundraiser, but canceled, Philly.com reported.