Biden, who was promoting his memoir, "Promise Me, Dad: A Year of Hope, Hardship and Purpose," was discussing how his son, Beau, the former attorney general of Delaware, convicted pediatrician Earl Bradley in 2017 of molesting infants.
A man in the audience stood up and said, "What about the girls you molested on C-Span at the Senate swearing in?"
C-Span (Cable-Satellite Public Affairs Network) is an American TV network that broadcasts proceedings by the US federal government, including occasional meetings between Biden and other government members of the public and their families.
Members of the crowd at the book singing swiftly began booing and shouting at the heckler.
"This is not Trump world," Biden responded, eliciting cheers.
Security eventually escorted the man out of the auditorium, according to Delaware Online.
The heckler, who was later identified on Twitter as PJ Howie, has previously accused Biden of sexual misconduct.
On June 11, Howie posted, "I found out about #JoeBiden molesting girls in October 2016. I have spent countless hours pulling clips from #CSPAN and posting them on Twitter. Here they are again. Please spread them far and wide."
Biden has been a voice for the "It's On Us" campaign, a national movement created by former US President Barack Obama and the White House Council on Women and Girls to raise awareness about sexual assault on college campuses.
In March, during an anti-sexual assault rally at the University of Miami, Biden said he would have "beat the hell out of" US President Donald Trump if they had gone to high school together.
"A guy who ended up becoming our national leader said, 'I can grab a woman anywhere and she likes it,'" Biden said at the rally. "They asked me if I'd like to debate this gentleman, and I said no. I said if we were in high school, I'd take him behind the gym and beat the hell out of him."
However, on March 28, Biden expressed his regret for saying what he did in an interview with Pod Save America.
"I shouldn't have said what I said," Biden said.
"Now, the idea that I would actually physically get in a contest with a President of the United States, or anybody else, now, is not what I said," Biden told the podcast. "It is not what this was about, but I should have just left it alone."