In 2006, Cain struggled with consistency, but showed signs of dominance in several starts, flirting with a no-hitter on more than one occasion. On April 24, Cain did not allow a base runner until the sixth inning in a win over the New York Mets. On May 21, Cain pitched his first complete game shutout, a one-hitter against the Oakland Athletics. On June 19, Cain pitched innings of no-hit ball against the Los Angeles Angels of Anaheim before finally surrendering a single to Chone Figgins.