Giuseppe Mastini, 60, who was given a life sentence in 1989, absconded while on day release from a high-security prison in Sassari, Sardinia.
Police launched a country-wide manhunt after he failed to return to the jail at midday on Sunday.
Mastini took advantage of a temporary release from the high-security jail in Sardinia to flee, failing to return to his cell on Saturday, the Polizia Equilibrio e Sicurezza (ES Polizia) union said.
Originally from Bergamo in northern Italy, Mastini moved to Rome in the 1970s with his family where he committed his first murder aged 11, according to Italian news agency ANSA.
Nicknamed Johnny lo zingaro or “Johnny the Gypsy” because of his Sinti origins, Mastini terrorised Rome during the 1970s and 1980s with a crimes including murder, kidnapping and burglary.
He first escaped from jail in 1987, when he failed to show up after a temporary release from prison.
He was on the run for two years, during which time he committed robberies, murdered a police officer, injured another, and took a young girl hostage.
After being caught and jailed again, he was given another temporary release in 2014 which was filled with “irregularities,” the union said, although it was unclear whether he actually escaped that time round.
But in June 2017, he once again escaped from a prison in northern Italy, following the same method.
Mastini’s escape gives criminals a “feeling of impunity”, Vincenzo Chianese, president of ES Polizia, told Italian media.
“Not only to prevent families of victims having to be warned every time this happens, thus renewing their pain, but also because the feeling of impunity in our country deeply undermines the credibility of the state.”