[5] He became involved in criminal activities immediately after arriving in the city,[3] joining[6] the newly formed Mayfield Road Mob.

[7] He and his brother Anthony quickly rose to positions of importance in the gang,[5] and Frank became involved in counterfeiting, murder, and various liquor law violations.

[8] While visiting family in Italy, Lonardo lost control of the Cleveland mafia to Salvatore "Black Sam" Todaro and Joseph "Big Joe" Porrello.

[9] Joseph Porello took over the crime family, but he began to be pushed aside by Frank Milano, who was by now head of a resurgent Mayfield Road Mob.

[10] Porrello began reasserting his power, and demanded that Milano turn over cash owed to him as well as make a large monetary payment as a sign of his loyalty.

On July 5, 1930, Porello and his bodyguard, Sam Tilocco, went to Milano's restaurant, the Venetian, at 12601 Mayfield Road in Cleveland's Little Italy neighborhood.

[14] Milano was also allegedly close to Mayfield Road Mob member N. Louis "Babe" Triscaro, who later became president of Local 436 of the International Brotherhood of Teamsters.

On April 21, 1931, he met in Cleveland with Frank Milano, Moe Dalitz, Meyer Lansky, Santo Trafficante Sr., and an emissary sent by Al Capone.

Milano was named a member of The Commission, alongside Joseph Bonanno, Al Capone, Tommy Gagliano, Lucky Luciano, Vincent Mangano, and Joe Profaci.

[24] While a member of the Cleveland crime family, he lived in Akron, Ohio, and made extensive real estate purchases there.

According to Alvin G. Sutton, Cleveland's top law enforcement officer, Milano smuggled individuals who had been deported from the U.S. back over the American border.

[26] When Wilbur Clark built the Desert Inn casino in Las Vegas, Nevada, in 1947, he sought and received capital from a group of gamblers and mobsters that included Moe Dalitz, Maurice Kleinmann, Thomas J. McGinty, Louis Rothkopf, and Sammy Tucker.

[30] According to the Chicago Sun-Times in 1966, cash skimmed from the casino (representing Milano's percentage interest in the operation) was delivered to him in Mexico City without going through others (such as Meyer Lansky).

[3] According to nightclub owner and former police officer Barney Ruditsky, Milano helped protect Cohen from being murdered by other crime families.