The "Oh no's" heard in offices around the country Friday likely came from Duke's upset loss to Mercer, where a No. 14 seeded team beat a 3 seed, 78-71.
Here comes the long-feared bracket-busting losses as tweeted by ESPN's Mike Humes.
Thursday wasn't much better with the beginning of the second round of the NCAA men's basketball tournament where both Ohio State University and the University of Oklahoma lost their games to lower seeded teams.
You can also throw in Harvard, a 12 seed beating a 5 seed, Cincinnati, as a likely bracket buster too. Of course, if you picked the upsets, you're sitting pretty.
But chances are your bracket is a mess going into Friday's games and the odds of winning the tournament pool are next to nil. But you joined millions of brackets that were busted.
The odds of winning Warren Buffett's $1 billion perfect bracket challenge, sponsored by Quicken Loans, were already listed at 1 in 9.2 quintillion. That's 92 with 17 zeros after it. Following Thursday's games, 83 percent of the nearly 9 million people with brackets in the challenge were eliminated. By the way, there is no record of a perfect bracket in the history of the NCAA tournament, according to reports.
(Read more: Your March Madness pool is probably illegal)
According to an ESPNU tweet Thursday, of the 11 million brackets filled out on ESPN, 94 percent were busted after the first four games were played.
(Full disclosure: a senior editor at CNBC.com ripped up his own printed bracket after OSU's loss. He had picked them to reach the Sweet 16. He also picked Oklahoma to beat North Dakota State, but to lose the next game. The bracket, now taped back together, remains at his desk and was not part of any office pool or the Buffett challenge, but for his personal use. He has vowed to skip next year's tourney—but he said that last year.)
Chances of a perfect bracket
A completely unscientific survey among two CNBC employees showed the effect of Thursday's games. (This was actually overheard in the kitchen line for coffee)
"I picked against Harvard, so I lost that game, and I didn't see North Dakota State winning, so that busted my bracket," said a mailroom worker at CNBC. "I'm kind of dead."
Hashtag Ohio (for Ohio State University) on Twitter showed some bitterness as well: "Your bracket is toast, send it to me, I'll make it official #MarchMayhem pic.twitter.com/8YFapD4QjT
Of course, the odds for picking a perfect bracket are not in your favor to begin with. In fact, most people have a greater chance of winning the lottery, shooting a hole-in-one in golf or being struck by lightning.
But while perfection would be great, the next best thing is just doing better than your fellow office worker and hoping their bracket busts sooner than yours. That may be the only way to get the odds in your favor.
This story has been updated to reflect that Duke was a No. 3 seed.
—By CNBC's Mark Koba. Follow him on Twitter @MarkKobaCNBC.