He made a successful transition to talking pictures in Warner Bros.' Tenderloin, speaking in a pleasant, slightly nasal tenor.

Stone was then typecast in streetwise roles, often playing a Runyonesque mobster or a gangland boss's assistant, notably as Rico Bandello's right-hand man Otero in the gangster classic Little Caesar (1931).

One of his most famous appearances was in the classic musical 42nd Street (1933), in which wiseguy Stone assesses a promiscuous chorus girl: "She only said 'no' once, and then she didn't hear the question!"

George E. Stone's most familiar role was "The Runt", loyal sidekick to adventurous ex-criminal Boston Blackie in Columbia Pictures' action-comedy series.

Stone was supposed to perform with Chester Morris in the first film of the series, Meet Boston Blackie, but was sidelined by a virus.

Stone's performances in the Blackies were well received, and he enthusiastically played scenes for laughs, doing dialects, disguising in women's clothes, posing as a child, or reacting in wide-eyed amazement or frustration to each story's twists and turns.

Both Chester Morris and George E. Stone reprised their screen roles for one year in the Boston Blackie radio series.

In the feature film The Man with the Golden Arm, Stone is the vindictive mobster who has been cheated at cards, and attacks dealer Frank Sinatra's friend Arnold Stang in a brutal fistfight.