With 3.9 second to go in the second overtime, Siena's Ronald Moore jumped into the spotlight.
From the same spot he hit a three at the end of the first overtime, Moore hit another one, but this time a game-winner to lead the Saints to a 74-72 victory over the Buckeyes.
Moore's clutch shots pushes Siena to a 27-7 mark on the season and the right to play number one overall Louisville on Sunday.
Evan Turner of Ohio State had one more shot to force a third overtime but missed as the clock expired.
Adding to the fortuitousness of Moore's shots, Ohio State coach had told his guys to foul him before he shot the ball in the first overtime. However, they failed to, and he hit the three to cause a second overtime.
On the game winner, he was supposed to pass the ball, but didn't since all his teammates were covered.
The small New York college has a history of surprising wins in the NCAA Tournament, having beaten Vanderbilt last year.
When Turner's shot rimmed out, Siena coach Fran McCaffrey ran up to his point guard and carried him off the court as Siena fans were chanting his name. Edwin Eublies had 20 points to lead the Saints, while Moore had 11 and Kenny Hasbrouck had 12 points and nine rebounds.
Ohio State had a 72-71 lead after Turner, who led the Buckeyes with 25 points, nine rebounds and eight assists, hit a driving layup with 17.9 seconds to go.
But Moore went up the right wing and calmly hit a three to put the Saints up 74-72.
The Buckeyes, though, let this game slip out of their hands as they had a 41-30 lead with 14:31 to go in the second half.
However, the Saints went on a 9-0 run putting the game at 41-39.