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.
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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.