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Guzik was born near Kraków, Galicia, Poland on May 20, 1886, and emigrated to the United States in the early 20th century. His parents were Jews from Katowice, Poland. Guzik later became involved in prostitution, and allegedly white slavery, in the South Side of Chicago's Levee vice district with his brother Harry, eventually driving rival Jack Zuta out of business. He later became a powerful political "fixer" operating from St. Hubert’s Old English Grill and Chop House, where Guzik received "bagmen" who delivered scheduled payoffs to various police precincts and city officials.
In the early 1920s, Guzik, supposedly overhearing a plan to murder Al Capone, informed him and later allied with the Chicago Outfit. Starting under Capone, Guzik was the trusted treasurer and financial wizard of the Outfit. Guzik worked for Capone, and later Paul "the Waiter" Ricca and Tony Accardo. Because Guzik was incapable of using a gun or killing anyone, Capone protected him, and once killed a man for him. In May 1924, Guzik got into an argument with a freelance hijacker named Joe Howard, who slapped and kicked him around. Incapable of physical resistance, Guzik related to Capone what had happened. Capone charged out in search of Howard and ran him down in Heinie Jacob's saloon on South Wabash Avenue, where Howard was bragging about the way he had "made the little Jew whine." When Howard saw Capone, he held out his hand and said, "Hello, Al." Capone instead grabbed Howard's shoulders and shook him violently, demanding to know why Howard had mistreated his friend. "Go back to your girls, you dago pimp," Howard replied. Capone then wordlessly drew a revolver and jammed it into his face, and after several seconds emptied it into him.
Capone quickly came to trust Guzik's advice in the various gang wars that developed as he tried to organize Chicago. Jake also served as the mob's principal bagman in payoffs to police and politicians, hence the origin of the nickname Greasy Thumb. Years later, as Capone was in failing health, it was Guzik who saw to it that Capone and his family never wanted for anything.
During the 1940s and 1950s, when the national syndicate was dominated by what was called the Big Six, it was Guzik and Accardo who flew east weekly to meet with the other heads of the organization: Joe Adonis, Frank Costello, Meyer Lansky and Longy Zwillman. The only serious legal problems that Guzik ever faced were with the IRS, and he eventually spent a few years in prison. At the Kefauver Committee hearings, he pleaded the Fifth Amendment on the ground that any response to the questions might "discriminate against me."
Guzik died of a myocardial infarction on February 21, 1956, while in bed at a South Side Chicago apartment he rented under the name Jack Arnold. He was 69. At his funeral services, more Italians were in attendance at the synagogue than ever before in its history.
Jake Guzik is a major figure in the 1959 television show The Untouchables, where he is portrayed by Nehemiah Persoff. Guzik was introduced in the first episode as the brains behind the Chicago Outfit after Al Capone's conviction, and ultimately appeared in six episodes.
Jake Guzik appears in the HBO show Boardwalk Empire where he is portrayed by Joe Caniano. His incident with Joe Howard was dramatized in an episode; here, Guzik's bullying coincides with Capone's son being bullied in school and it is the similarities between the two incidents that drives Capone to kill Howard.