In the NCAA Tournament, the matchups between the No. 5 seeds and No. 12 seeds are always interesting. It seems like there’s always at least 1 upset where a 12-seed advances.

Why is that? Well, the 12-seeds are often the best of the teams that automatically qualify for the tournament — smaller schools that win their conference tournaments. Those schools get the 12-16 seeds, with the best of the group earning 12 seeds.

Meanwhile, 5-seeds are often good, but not great, major conference teams. Indeed, that holds true this year. The 4 5-seeds are:

  • Villanova (Big East)
  • Tennessee (SEC)
  • Colorado (Pac-12)
  • Creighton (Big East)

All good teams, yes, but all very flawed. The 12 seeds are mixed — a pair of surprising major conference champions and a couple of sneaky-good smaller-conference champs. They are:

  • Oregon State (Pac-12)
  • Georgetown (Big East)
  • Winthrop (Big South)
  • UC-Santa Barbara (Big West)

At least 1 of those 12 seeds will win, statistically speaking. In 2019 (the last NCAA Tournament), 3 of the 12 seeds won. In 2018, the 12 seeds went 0-4. One won in 2016. Zero won in 2015. Three won in 2014.

You get the picture. It’s probably a wise bet to pick at least 1 12 seed in this year’s tournament to advance to Round 2. But which matchup should you target?

Let’s break down the 4 5 vs. 12 matchups in this year’s NCAA Tournament and which ones are most likely to provide an upset.

Click here to sign up with FanDuel Sportsbook and grab a $1,000 risk-free bet and no-brainer bet on Michigan State.

No. 5 Villanova vs. No. 12 Winthrop

TV info: Friday at 9:57 p.m. ET on TNT

Chance of an upset: 75%

I’m predicting this upset to happen. I know it’s a popular one among analysts and fans, but there’s a reason for it. It’s not Villanova’s fault, but the Wildcats are dealing with a couple of crucial injuries.

Collin Gillespie tore his MCL recently. Meanwhile, Justin Moore is dealing with an ankle sprain. Gillespie (14.0 points, 4.6 assists, 3.3 rebounds and 1.0 steals per game) and Moore (12.6 points, 4.1 rebounds and 2.9 assists per game) are key players for Jay Wright’s squad.

Meanwhile, Winthrop only lost 1 game all year in the Big South. The Eagles have 4 players who average at least 10 points per game, led by senior forward Chandler Vaudrin (12.2 points, 7.2 rebounds, 6.9 assists, 1.3 steals per game). Vaudrin truly does it all, and he’s going to be a tough matchup for a team that might be down 2 key players.

Give me the Eagles to advance here. They could make life difficult for Purdue (or North Texas) in Round 2, too.

No. 5 Creighton vs. No. 12 UCSB

TV info: Saturday at 3:30 p.m. ET on TruTV

Chance of an upset: 49%

Neither team plays at a particularly fast pace. But the Gauchos are red-hot entering the NCAA Tournament and have won 5 games in a row. They weren’t particularly challenged too much in the Big West Tournament. And they have a sharpshooter you need to know. His name is JaQuori McLaughlin and he hits 40.4% of his 3s:

He averages 16.2 points, 5.2 assists, 3.4 rebounds and 1.6 steals per game as the Gauchos’ biggest impact player. Meanwhile, Creighton just got blown out by Georgetown in the Big East Tournament final.

Creighton has some good players, too. Marcus Zegarowski is a star, averaging 15.5 points, 4.3 assists, 3.7 rebounds and 1.3 steals per game. He also makes 41.2% of his 3s. That sounds pretty similar to McLaughlin, right?

Whichever sharpshooting guard gets his team off to the hotter start could decide this game. I have it as a toss-up. I’ll give the ever-so-slight edge to the Blue Jays, though.

No. 5 Colorado vs. No. 12 Georgetown

TV info: Saturday at 12:15 p.m. on CBS

Chance of an upset: 30%

I think Colorado is a weak 5-seed, but I also think Georgetown’s magic is about to end. The Hoyas won’t be able to recapture the energy of the Big East Tournament, with coach Patrick Ewing returning to Madison Square Garden, where he had so many great memories as a New York Knicks star.

Remember, this team finished 8th in the Big East during the regular season and would have had an overall record of 9-12 if not for a 4-game winning streak to win the conference tournament.

Meanwhile, Colorado made it to the Pac-12 Tournament title game before losing to red-hot Oregon State, which we’ll discuss next. As long as McKinley Wright IV is his usual do-it-all self (15.5 points, 5.6 assists, 4.3 rebounds and 1.1 steals per game), the Buffaloes should stampede past the Hoyas. But, if Jahvon Blair continues his hot play, the Hoyas will at least have a chance to pull off the upset.

No. 5 Tennessee vs. No. 12 Oregon State

TV info: Friday at 4:30 p.m. ET on TNT

Chance of an upset: 5%

I’m not saying this because I write for an SEC site. Rather, I legitimately just don’t believe in the Beavers. Yes, the Vols have been an inconsistent squad all year, but the Beavers were the No. 5 seed in the Pac-12 Tournament before their impressive run to the title.

If this game were played right after the Pac-12 Tournament ended, I’d give the Beavers more of a chance. But Oregon State got hot in Las Vegas and made a run. Now, the Beavers have had nearly a week to cool off. Plus, they’re in a different part of the country.

The Vols, meanwhile, have won 2 games against Florida lately and took Alabama to the wire in the SEC Tournament semifinals. I think the Beavers’ magic is long gone and the Vols will win this game comfortably.

Click here to get BetMGM and get $10 free for all 16 NCAA Tournament games on Friday or Saturday.