Cross-discipline and cross-cultural training aided Berberian in the formation of her own broad tastes. At Columbia University and New York University, she exposed herself to literature, mime, and the dances of Iberian, Armenian, and Middle East cultures, among other subjects. Following voice training with Giorgina del Vigo in Milan, she made her debut in 1957 at a concert of contemporary music in Naples. Identified as a musical and technically secure interpreter of vocally treacherous works of the day, she was invited to Rome to perform on a program of music by John Cage the next year. Her first American appearance as a professional singer took place at the Tanglewood festival in 1960; she perfomed in Berio's Circles, one of a series of works written to take advantage of her remarkable technical brilliance and her riveting presence on the concert stage. Fame overtook her quickly, and she became the preferred interpreter of works written specifically for her by the likes of Sylvano Bussotti, Hans Werner Henze, and Igor Stravinsky. Many such works proved all but unperformable by anyone else. Tragically short-lived, Berberian left a recorded legacy that displays her all-encompassing interests. In addition to the expected works by Berio and Cage, she recorded a number of folk songs, "Summertime" from Gershwin's Porgy and Bess, and a powerfully affecting Ottavia in Nikolaus Harnoncourt's edition of Monteverdi's L'incoronazione di Poppea. Her anguished farewell to Rome holds both great feeling and poised vocalism and is one of the high moments in the performance.
In addition to her performing skills, Berberian was a composer of some note. Her Stripsody, written in 1966, reveals both humor and the ability to exploit her own virtuosity as a performer.