DeAndre Kane drove for the game-winning layup with 1.6 seconds left and No. 3 seed Iowa State beat North Carolina 85-83 on Sunday, advancing to the Sweet 16 for the first time since 2000.
The Cyclones (28-7) head to Madison Square Garden next week to face No. 7 seed Connecticut in the East Regional semifinals.
The Tar Heels (24-10) are gone in the NCAA tournament's opening weekend for the first time in consecutive seasons under coach Roy Williams.
North Carolina's Nate Britt raced the ball up court after Kane's basket, but time expired before he could reach halfcourt and call a timeout. Officials huddled for several minutes reviewing clock replays before ruling the game was over.