At a press conference Saturday afternoon, Chief of Detectives Dermot Shea announced Comello's arrest, but said such issues as motive and possible accomplices were still under investigation.
A man has reportedly been arrested in connection with the killing of Francesco "Frank" Cali, the alleged leader of the notorious Gambino crime family.
The brazen killing was the first slaying in more than 30 years of a New York City crime boss.
The 53-year-old Cali, who was shot to death on Wednesday outside his Staten Island home, was allegedly the head of the Gambino family, one of the five Italian-American Mafia families that have historically dominated organized crime in NY and New Jersey.
Detectives have recovered a truck they think was involved but not the firearm used in the shooting, Shea said.
"We do not believe this was a random act".
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Shea said there was "extensive video footage" recovered from the house where the shooting occurred. He was rushed to Staten Island University Hospital North, where he was pronounced dead.
When asked about the suspect's arrest record, Shea said he "crossed paths in some limited circumstances with the NYPD", including getting a parking ticket on Staten Island the day Cali was killed.
Federal prosecutors referred to Cali in court filings in recent years as the underboss of the Mafia's Gambino family, once one of the most powerful crime organizations in the country.
Cali's only mob-related criminal conviction came a decade ago, when he pleaded guilty in an extortion scheme involving a failed attempt to build a NASCAR track on Staten Island.
Cali was sentenced to 16 months in prison and was released in 2009.
The killing marked the first murder of a sitting mob boss in NY since the December 1985 hit on Gambino boss Paul "Big Paul" Castellano, who lived in the same neighborhood where Cali was shot. He was set up by John G. Gotti who then took over the Gambino family.
Gotti died in prison of cancer in 2002.