Roberto Pannunzi was detained in Bogota with a fake Venezuelan identity card in a joint operation by Colombian police together with the US Drug Enforcement Administration (DEA).
"He is the biggest cocaine importer in the world," said Nicola Gratteri, deputy chief prosecutor in Reggio Calabria in southern Italy.
"He is the only one who can organise purchases and sales of cocaine shipments of 3,000 kilos (6,600 pounds) and up," he said.
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"Pannunzi is the only one who can sell both to the 'Ndrangheta and to Cosa Nostra. He is definitely the most powerful drug broker in the world," he said.
The 'Ndrangheta is based in Calabria and is a major player in international drug trafficking. The Sicilian mafia is known as Cosa Nostra.
Gratteri said Pannunzi was being deported since "an extradition order would have taken several months".
He is expected to land at Rome's Fiumicino airport later on Saturday.
In April, Colombia captured another suspected top mafioso, Domenico Trimboli, alleged to be a lynchpin between the Medellin drug cartel and the 'Ndrangheta.
Pannunzi had escaped from a Rome clinic where he was being held under house arrest in 2010 -- repeating an earlier escape in the same way in 1999.
He was previously been detained in Colombia in 1994, when he reportedly offered the arresting officers a million dollars in cash to walk away.
Gratteri said that during Friday's arrest, Pannunzi had told the police he was ill but he said he hoped the alleged trafficker would not be granted house arrest in a hospital in Italy again.
"I hope that he is not given house arrest a third time because he could attempt a third escape."
"It's exhausting having to go around the world to find him every time he escapes," Gratteri said.
 AFP