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When Fanning was a small child, she was an actress at the Towne Lake Arts Center in Woodstock, Georgia, starring in small plays.
The two sisters were replaced; Abigail Breslin took on the lead role as Anna Fitzgerald, and Sofia Vassilieva was cast as Kate Fitzgerald.
In 2001, Fanning was chosen to star opposite Sean Penn in the movie I Am Sam, the story of a mentally challenged man who fights for the custody of his daughter (played by Fanning).
Her role in the film made Fanning the youngest person ever to be nominated for a Screen Actors Guild Award, being seven years of age at the time.
The film was generally panned, and critic Chuck Wilson called it "a fascinating meeting of equals – if the child star [Fanning] challenged the master [De Niro] to a game of stare-down, the legend might very well blink first." Fanning voiced Lilo Pelekai (taking over for Daveigh Chase) in the direct-to-video film Lilo & Stitch 2: Stitch Has a Glitch.
She also had a small part in the Rodrigo García film Nine Lives (released in October 2005), in which she shared an unbroken nine-minute scene with actress Glenn Close, who had her own praise for Fanning: "She's definitely an old soul.
In 2004, Fanning appeared in Man on Fire as Pita, a nine-year-old who wins over the heart of a retired mercenary (Denzel Washington) hired to protect her from kidnappers.