Aside from his role in the American Mafia, he is also notorious for the reason that G. Robert Blakey and others have alleged that Carlos Marcello, Santo Trafficante Jr., and Sam Giancana conspired in the 1963 assassination of U.S. President John F. Kennedy in retaliation for federal investigations and prosecutions that threatened both the power and the multibillion-dollar profits of organized crime.

[4] With his family, Marcello immigrated to the United States in 1911 and settled in a decaying plantation house near Metairie in Jefferson Parish, a suburb of New Orleans.

He was later imprisoned for masterminding a crew of teenage gangsters who carried out armed robberies in the small towns surrounding New Orleans.

[citation needed] On his release from prison, Marcello became associated with Frank Costello, the leader of the Genovese crime family, in New York City.

According to former members of the Chicago Outfit, Marcello was also assigned a cut of the money skimmed from Las Vegas casinos, in exchange for providing "muscle" in Florida real estate deals.

By this time, Marcello had been selected as "The Godfather" of the New Orleans Mafia, by the family's capos and with the approval of The Commission after the deportation of his predecessor, Sylvestro Carolla, to Sicily.

On March 24, 1959, Marcello appeared before the United States Senate's McClellan Committee investigating organized crime.

[8] On April 4, 1961, the U.S. Justice Department, under the direction of Attorney General Robert F. Kennedy, apprehended Marcello as he made what he assumed was a routine visit to the immigration authorities in New Orleans, then deported him to Guatemala.

However, in October 1964, Marcello was charged with "conspiring to obstruct justice by fixing a juror [Rudolph Heitler] and seeking the murder of a government witness [Carl Noll]".

[14] In 1981, Marcello, Aubrey W. Young (a former aide to Governor John J. McKeithen), Charles E. Roemer, II (former commissioner of administration to Governor Edwin Edwards), and two other men were indicted in the U.S. District Court for the Eastern District of Louisiana in New Orleans with conspiracy, racketeering, and mail and wire fraud in a scheme to bribe state officials to give the five men multimillion-dollar insurance contracts.

[16] U.S. District Judge Morey Sear allowed the admission of secretly-recorded conversations that he said demonstrated corruption at the highest levels of state government.

[19] In its investigation, the HSCA noted the presence of "credible associations relating both Lee Harvey Oswald and Jack Ruby to figures having a relationship, albeit tenuous, with Marcello's crime family or organization".

They claim that their book lays out evidence that has been corroborated by additional sources and official records released in subsequent years.

[24] According to Waldron, Marcello admitted his involvement to two other inmates during a fit of rage in the prison yard at the Federal Correctional Institution in Texarkana, Texas.

[2] According to Waldron, Marcello arranged for two hit men to carry out the assassination after entering the United States from Canada and Europe, while setting up Oswald as the fall guy and ordering the subsequent murder of various conspirators and witnesses who risked turning informants, including mobsters Johnny Roselli and Sam Giancana.