Holmes left college a year early and was taken in the first round (25th overall) of the 2006 NFL Draft by the defending Super Bowl XL champion Pittsburgh Steelers. The 25th pick overall, he was the first receiver since Plaxico Burress taken in the first round by the Steelers. The Steelers traded up with the New York Giants from 31st to draft Holmes. Holmes, who wore number 4 at Ohio State (a number that isn't issued to wide receivers in the NFL), was issued number 10, previously worn in Pittsburgh by former kicker Roy Gerela and quarterback Kordell Stewart.