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Born in Rome, Guelfi studied law before turning to vocal studies in Florence with baritone Titta Ruffo and later in Milan with baritone Mario Basiola. He made his stage debut in Spoleto, as Rigoletto in 1950. He made his debut in 1952 at the Teatro alla Scala in Milan, also appearing in Venice, Florence, Rome, Naples, Palermo, Catania, and becoming a regular guest at the Arena di Verona. Outside Italy he appeared in Berlin, Lisbon, London, Buenos Aires, Rio de Janeiro, Madrid, and Cairo. He made his American debut in 1954 at the Lyric Opera of Chicago, and at the Metropolitan Opera of New York in 1970. He took part in the creation of contemporary works including Lazzaro in Pizzetti's La figlia di Jorio, Naples, 1954. He was mostly known for his Verdi portrayals in operas such as Nabucco, I due Foscari, Attila, Macbeth, Il trovatore, I vespri siciliani, La forza del destino, and Aida. He also appeared in verismo operas such as Cavalleria rusticana, Andrea Chénier, Tosca, and La fanciulla del West.
He sang the role of Rance in La fanciulla del West in a recording with Renata Tebaldi, conducted by Arturo Basile, and was in the 1961 Tokyo's performances of Tosca, also with Tebaldi, on DVD.
- "Scomparso il baritono Giangiacomo Guelfi, aveva debuttato a Spoleto con il Rigoletto". SpoletoCity (in Italian). 9 February 2012. Archived from the original on 12 February 2012. Retrieved 10 February 2012.
- "Obituary:Giangiacomo Guelfi". Opera News. May 2014.