John and his twin sister Manuela were born in Berkeley, California, on August 24, 1943. Cipollina attended Tamalpais High School, in Mill Valley, California, as did his brother, Mario (born 1954), and sister, Antonia (born 1952). Their father, Gino, was of Italian ancestry (Genovese and Piemontese origins).
He was a realtor, and their mother, Evelyn, and godfather, José Iturbi, were concert pianists.
John showed great promise as a classical pianist in his youth, but his father gave him a guitar when he was 12 and this quickly became his primary instrument.
Cipollina had a unique guitar sound, mixing solid state and valve amplifiers as early as 1965. He is considered one of the fathers of the San Francisco sound, a form of psychedelic rock.

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