Kupcinet, the daughter of Chicago Sun-Times columnist Irv Kupcinet, starred in a handful of minor roles, including a small part in the 1961 Jerry Lewis film The Ladies Man.

She was last seen alive on the night of Wednesday, November 27, the day before Thanksgiving. Her nude body was found on Saturday November 30 on her couch in her West Hollywood apartment. The coroner concluded that she had been dead about three days. Due to a broken hyoid bone in her throat, the cause of death was officially listed as strangulation. Writer James Ellroy suggests that Kupcinet committed suicide with an overdose of pills, but his conclusion is rejected by her family.

Police questioned several of Kupcinet's friends, her neighbor David Lange, and her boyfriend, actor Andrew Prine, multiple times but no charges were ever filed.

The connection to JFK's assassination was first made by author Penn Jones. An Associated Press story reported that an operator overheard a female caller from the area of Oxnard, California say "The President is going to be killed" about 20 minutes before the assassination. Jones, in his book Forgive My Grief II, moved the call 50 miles south to Los Angeles and the date of Kupcinet's death to November 24 and claimed that Kupcinet was the caller. Other authors, while often correcting Jones' errors, have also claimed Kupcinet's death was related to the JFK assassination, but left unexplained is why she would call from Oxnard and how she had advance knowledge of the assassination.

After her name appeared on a 1992 Today Show broadcast on a list of "mysterious deaths" connected to the JFK assassination, her father wrote in his February 9 column that linking her to JFK’s killing was "an atrocious outrage...Karyn no longer can suffer pain by such an inexcusable mention, but her parents and her brother Jerry can."