In order to advance to the Elite Eight, SU will have to pull off by far the biggest upset of the Sweet 16.
Duke is the only double digit favorite of the round, nearly doubling the line of any other match-up.
The Blue Devils are justifiably heavy favorites, after winning their first two games of the tournament by 22 and 25 points.
The Dukies also beat the Orange by 16 a month ago, despite going 2-18 from 3-point range and scoring a season-low 60 points.
Syracuse held high scoring teams Arizona State, TCU, and Michigan State each under that 60 point threshold to get to this point, and the 2-3 zone will once again be key for the Cuse to continue their Cinderella run.
While Duke scored 176 points in their 2 wins last weekend, the Orange allowed just 161 points in their 3 wins.
Kansas and Clemson get things started from Omaha just after 7 tonight, and then SU-Duke follows on CBS.