Franco De Grandis was born in Turin and studied voice and piano at the city Conservatory. In 1981, he won the As.li.co. Competition. He went on to enter the Maria Callas Competition in Rome in 1983, which was also the year of his debut at Milan's Teatro alla Scala in Turandot (Timur), conducted by Lorin Maazel. This marked the beginning of an international career that would bring him to work with major orchestra conductors and at the most prestigious opera houses.
After performing in Salzburg in 1985 in the production of Don Carlos, directed by Herbert von Karajan, and then in Tosca the following year, De Grandis was invited to La Scala in Milan, where he appeared in the production of Guglielmo Tell conducted by Riccardo Muti. He debuted at the New York Metropolitan Opera House in Il Trovatore alongside Luciano Pavarotti, conducted by Richard Bonynge, and performed at the Vienna Staatsoper, the Grand Théâtre in Geneva and the Municipal Theatre in Florence.
His repertoire includes a wide variety of roles, such as Sparafucile in Rigoletto, Ramfis in Aida, Colline in La Bohème, and Basilio in Il Barbiere di Siviglia. He has also appeared in Don Carlos, Luisa Miller, Simon Boccanegra, Macbeth, Samson et Dalila and Spontini's Vestale. His concert repertoire includes Verdi's Requiem and Mozart's Requiem.
In the 1996/97 season he appeared as Sparafucile in Rigoletto in Venice, at the Théâtre du Capitole in Toulouse and at the Arena di Verona (where he also played Ramfis in Aida). He played Banquo in Macbeth at the Municipal Theatre in Treviso and at the Municipal Theatre in Rovigo, and Fiesco in Simon Boccanegra at the Theatre in Messina. In Santiago, Chile, he was a soloist in Verdi's Requiem.
For the 1997/98 season, he appeared in Massenet's Roméo et Juliette at the Washington Opera, and in Rigoletto at the Bellini Theatre in Catania, debuting in the role of Oroveso in Norma, performed in Messina. Every year, he has also played the role of Ramfis in Aida at the Arena di Verona.
In 1999 he played Sparafucile at the Opéra in Nice. In 2000 De Grandis debuted in Stravinskij's The Rake's progress at the Bellini Theatre in Catania and was a soloist in the Bologna performance of Verdi's Requiem, also participating in the tour of the Arena di Verona Opera Company in China. In 2001 he played Zaccaria in Nabucco, Ferrando in Il Trovatore and Banquo in Macbeth, performing in Dresden, Copenhagen and Messina. He subsequently appeared in La Forza del destino, Don Giovanni, Guglielmo Tell, Mephistofele and Boris Godunov. In 2003 De Grandis played the role of Ferrando in Il Trovatore at the Opera House in Cagliari, and in 2004 he was Sparafucile in Rigoletto at the Arena di Verona.