Lombardo formed the Royal Canadians in 1924 with his brothers Carmen, Lebert and Victor, and other musicians from his hometown. They billed themselves as creating "the sweetest music this side of Heaven." The Lombardos are believed to have sold between 100 and 300 million records during their lifetimes, many featuring the band's lead singer from 1940 onward, Kenny Gardner.
Lombardo was born in London, Ontario, Canada, to Italian immigrants Gaetano Alberto and Angelina Lombardo. His father, who had worked as a tailor, was an amateur singer with a baritone voice and had four of his five sons learn to play instruments so they could accompany him. Lombardo and his brothers formed their first orchestra while still in grammar school and rehearsed in the back of their father's tailor shop. Lombardo first performed in public with his brother Carmen at a church lawn party in London in 1914. His first recording session took place where cornetist Bix Beiderbecke made his recordings—in Richmond, Indiana, at the Gennett Studios—both during early 1924.[citation needed]
After that solitary Gennett session, they recorded two sessions for Brunswick; a rejected session in Cleveland in late 1926, and an issued session for Vocalion in early 1927. The band then signed to Columbia and recorded prolifically between 1927 and 1931. In early 1932, they signed to Brunswick and continued their success through 1934 when they signed to Decca (1934–35). They then signed to Victor in later 1935 and stayed until the middle of 1938 when again they signed to Decca. In 1938, Lombardo became a naturalized citizen of the United States. Between 1941 and 1948, their sister Rose Marie, the youngest of seven siblings, joined the Royal Canadians as the band's first and possibly only female vocalist.

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