On June 24, 2007, he made his major league debut against the New York Mets, as a pinch hitter for pitcher Jay Marshall.

Leading off the top of the eighth, Melillo was walked by Guillermo Mota in his only major league plate appearance and game.

On June 5, 2008, Melillo was traded by Oakland to the Toronto Blue Jays for cash considerations and was assigned to the Triple-A Syracuse Chiefs.

Less than a week later, he signed a minor league contract with the Milwaukee Brewers and was assigned to the Double-A Huntsville Stars.

[5] He played 46 games for the Angels triple-A affiliate in Salt Lake City, hitting .284, and thereafter retired from professional baseball.