Mafalda Favero was born in Portomaggiore, near Ferrara. When she was 17, she started studying with Alessandro Vezzani at the Conservatory in Bologna and attracted the notice of Franco Alfano. She began her professional career in her early 20s in Cremona, then moving to Parma where she sang several roles, before eventually getting to La Scala where she debuted singing Eva in Die Meistersinger von Nürnberg under Arturo Toscanini in 1929.
She remained one of the regular singers at La Scala until 1950, also singing in London (Royal Opera House) in 1937 and 1939, and in the United States (Metropolitan Opera and San Francisco Opera) in 1938. She had a large repertoire, including many contemporary works. She sang in the first performances of Alfano's L'ultimo Lord, Mascagni's Pinotta, Zandonai's Farsa amorosa, and Wolf-Ferrari's Il campiello and his operatic adaptation of de Vega's play La dama Boba.
Attracted to the role of Puccini's Madama Butterfly, she later blamed this for her early retirement in 1954: "The role of Cio-Cio-San was my ruination. To sing it as I did, giving everything I had and then some, exacted an enormous price. I am quite aware that Butterfly cut short my career by at least five years".
Giulietta Simionato remarked on her "animal sensuality" and said "She gave away a great deal of herself – more than was good for her – but the result was extremely moving."
She died in Milan in 1981, aged 78.
Preiser have published a collection of her recordings on CD in their Lebendige Vergangenheit series (Mono 89162). This contains the 1937 'Cherry Duet' (Suzel, buon di) with Tito Schipa from Mascagni's L'amico Fritz, one of the glories of the gramophone.
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