Workers have discovered human bones at the Holy See Embassy to Italy and police are investigating the matter, the Vatican said on Tuesday.
Italian media said forensic scientists were looking to see if the remains might be those of Emanuela Orlandi, the 15-year-old daughter of a Vatican employee who vanished in 1983.
The Vatican said in a statement that the bone fragments were discovered during restructuring work on an annex to the Holy See's imposing embassy compound near Rome's famous Villa Borghese museum.
It said chief prosecutor Giuseppe Pignatone was leading the investigation and had tasked forensic specialists with determining the "age, sex and date of death" of the body.
Orlandi's fate is one of the biggest mysteries in modern Italian history.
Her disappearance was initially linked to a possible attempt by unknown persons to win freedom for Mehmet Ali Agca, the Turkish gunman who shot Pope John Paul II in 1981 and was then serving a life sentence in an Italian jail.
In 2005, an anonymous caller to a television talk show said the secret to her kidnap was buried along with Enrico “Renatino” De Pedis, a mobster who once led the feared Magliana gang which terrorised Rome in the 1980s.
Police eventually opened his tomb in a Rome basilica in 2012 looking for clues but came up empty handed.
The Vatican statement made no mention of Orlandi.