In dramatic scenes, military police made the arrests in a dawn raid in Corleone, a small hill town in Sicily that has been synonymous with the Mafia for decades.
So much so that the town's reputation has transcended onto the silver screen. It's the birthplace of several fictional characters in The Godfather, most notably Vito (Andolini) Corleone.
Police say that the six suspects in custody were intent on adding to the town's violent history.
They claim intelligence gleaned by wiretapping the phones of mafia members, revealed that there were plans to kill Mr Alfano, one of Italy's highest ranking cabinet officials, and a Sicily-born minister, during an electoral rally in Sicily.
A source told Reuters that one Cosa Nostra ('Our Thing') gang member was recorded being very explicit.
"If it's all agreed, we'll hit him, right in the head."
Mr Alfano has been calling for jail sentences for people convicted of mafia association to be toughened.
Italy already has a stringent Article 41-bis prison regime, which isolates inmates completely.
Mafia Family back in Sicily pic.twitter.com/6H8dmuyBYK— Robert Ferguson (@robferguson101) November 19, 2015
One convict imprisoned in these conditions is the very colorful and ruthless Mafia king Salvatore "Toto" Riina. All six suspects are linked to Mr Riina, nicknamed "The Beast" for his ruthlessness and brutality.
Once the "capo di tutti capi" (boss of bosses) of the powerful Corleonesi faction of the Mafia, Riina is serving multiple life-sentences after being convicted of several murders, including the assassination of rival gangsters.
Italian politicians have sent Mr Alfano messages of support in response to the news. Defense Ministry Undersecretary Gioacchino Alfano said "threats don't frighten people like Angelino Alfano, who have always stood firm against organized crime."
"We are all with Alfano against all mafia."