How much of a difference will history and tradition make? Thirteen of the teams have played in a Final Four. Gonzaga, Missouri and Xavier never have won a regional championship.
Will it be another chalk-filled Final Four? Last season was the first in which all four top seeds made the Final Four. This year, all four ( UConn, UNC, Pitt, Louisville) are alive. In fact, the top three seeds in each region are in the Sweet 16 for the first time.
Which team can pull off the big upset? Purdue hasn't gotten much run, but the Boilermakers are hot (five straight wins), and UConn is playing without the injured Jerome Dyson and may be distracted (see more below).
South RegionalWill Ty Lawson's toe hold up? Without Lawson last Saturday, the top-seeded Tar Heels may have lost to LSU. Lawson said that during Saturday's game, the world's most-talked-about toe felt "about a 6 or 7" on a scale of 10.
How will Oklahoma handle Syracuse's 2-3 zone? Dominating Blake Griffin (22.5 ppg, 14.4 rpg) says the Sooners just need to be smart on offense, but they will need to hit shots over the zone. If they don't, it'll be an Orange crush on Griffin.
Can Gonzaga get over the hump? Are the Zags really mid-majors anymore? They've consistently made runs in the tourney, but to be considered among the elite, they need to take the next step by beating North Carolina. Good luck with that.
East RegionalCan Duke handle Villanova in the paint? Here's a stunner: a guard-oriented Duke team. The Blue Devils' lack of a serious inside threat could be a problem against the Wildcats' Dante Cunningham (16.3 ppg, 7.3 rpg).
When does the real Pitt show up? The Panthers survived East Tennessee State and Oklahoma State, but a similar effort tonight likely means the Panthers will be Musketeered right out of the tournament.
Road sweet road? Duke and Villanova had the benefit of essentially playing at home in the first two rounds. Now, which of these teams will man up on the road (Villanova is 9-4 on the road this year, Duke 7-6)?
Midwest RegionalCan Arizona's defense handle Louisville? Nevermind that the Wildcats shouldn't be in the tourney. Focus on the fact they play a poor 1-1-3 defense and the Cardinals are deadly behind the arc (39.1 percent on 3s).
Can Kansas pass its first test? North Dakota State and Dayton? Not exactly a gauntlet in the first two rounds. Up next, a Michigan State team that whipped the Jayhawks 75-62 on Jan. 10.
Will Michigan State score enough? Yes, the Big Ten is boring, err, a great defensive conference. The Spartans are nasty on defense and on the glass. One problem here: MSU was 2-5 in the regular season when allowing 70 points.
West RegionalCan Memphis handle Missouri's press? Missouri's full-court defense is even better than Maryland's (Mizzou is second in the nation in steals). Memphis starting guards Tyreke Evans and Antonio Anderson average a combined seven turnovers per game.
Will Connecticut be distracted? Talk about the worst time for hearing about alleged NCAA violations. The Huskies will have to block that out against a sizzling Purdue team that plays solid defense.
Who wins the Clash of the Chalk Titans? Look for the top two seeds to advance, as No. 1 UConn and No. 2 Memphis are hot (especially the Tigers with a 27-game win streak). That regional final would be an all-out war.