He died of complications from lung cancer, according to David Poppe of Ruane, Cunniff & Goldfarb, of which Ruane was chairman. At the time of his death, he also was co-manager of the Sequoia Fund.

Ruane and partner Richard T. Cunniff founded their investment management firm in 1969 after raising $20 million from investors. Most of their customers came to them on the recommendation of Warren Buffett, Ruane's former classmate and close friend.