The Commodores haven't had too many other SEC teams' numbers over the years, but they have a chance Saturday to pull off a rare feat: beat the same conference foe three straight times, something they haven't done since beating Kentucky five times in a row from 1991-1995.
The prospective victim is Ole Miss, reeling from a 16-10 loss to South Carolina that exposed many weaknesses, most notably in the offensive line and in quarterback Jevan Snead.
Overall, Vanderbilt has won two straight and three of the last four match-ups between the teams, most recently a crazy 23-17 victory in Oxford last season where Ole Miss committed six turnovers.
That being said, the Rebels are out to avenge that frustrating defeat, and recent history shows they are more than capable of bouncing back from disappointment; a week after coughing up a win against the Commodores, they handed the eventual national champion Gators their only loss of the season.
So, it's going to be quite a battle Saturday at Vanderbilt Stadium between two rivals from the East and West divisions searching for their first conference win.
Here are five keys to Vanderbilt making it a hat trick against the Rebels.
1) Get up in Snead's grill
Despite his struggles, Snead is still a very good quarterback. He's got both a strong and accurate arm and a good physique. However, put pressure on any quarterback and he's going to not be on his game.
Look no further than last year.
"We usually throw a lot at quarterbacks," said Vanderbilt coach Bobby Johnson. "It wasn't all his fault."
Johnson's right; it's also the offensive line's job to protect Snead and they did a poor job of doing so last year.
If the Commodore defensive line gets as much penetration in the backfield as the Gamecocks did last Thursday, Snead might be in line for another turnover fest like last season against the Commodores when he threw four interceptions, including one returned for a touchdown.
The secondary played within themselves and made plays when they were available, and defensive coordinator Bruce Fowler did a great job of sending mixed blitz packages to wreak havoc on the beleaguered Snead.
Do that again Saturday with success, and it could be another long day for No. 4.
2) Deny Dexter
Flanker Dexter McCluster is very dangerous out of Ole Miss' famous Wild Rebel formation. He was about the only semblance of an offensive spark the Rebels had against the Gamecocks, and his speed could provide problems for Vanderbilt's linebackers, better known for their strong tackling than their quickness.
He needs to be prevented from making big plays. Stacking the box with him in and spreading the linebackers out to stop him from getting around the edge will be significant.
Containing McCluster will put added pressure on Snead to perform, something he's really yet to do this season.
3) Special teams perfection
As I've said before, Vanderbilt's offense gives them a very small margin for error.
So special teams execution really needs to be flawless if the Commodores want to win this game.
That means solid coverage units, making field goals and continued strong play from punter Brett Upson, whose rugby-style kicking is generally effective at pinning opponents downfield.
4) Get the tight ends involved in the passing game
In their last two conference games, the Commodores have spent roughly 38 minutes per contest playing defense.
That's un-flipping-acceptable. The fact that they lost both games by double digits shouldn't come as too big of a surprise. A defense gasping for air couldn't stop fourth-quarter touchdowns that put the game out of reach both times.
While establishing the run is important for Vanderbilt, what will be more important will be putting quarterback Larry Smith in position to succeed by making use of the Commodores' two big targets at tight end, Austin Monahan and Brandon Barden.
Short, intermediate pass plays with a high-percentage chance of completion will help move the chains and get the Vandy D some much-needed downtime, while simultaneously making the Ole Miss D work that much harder.
The Vanderbilt receiving corps is still a work in progress. Monahan and Barden are proven weapons and the coaching staff needs to take advantage of that.
5) Offensive line: You need to step up
Maybe nothing is more important than Vanderbilt's offensive line rising to the challenge against the powerful defensive line of the Rebels.
Center Bradley Vierling vocalized the challenge he and his four compatriots in the trenches will face.
"Their front four is big and athletic," he said. "Probably the fastest team on defense that we've played against so far."
Marcus Tillman, Kentrell Lockett, Ted Laurent and Lawon Scott, the Ole Miss starters, are all upperclassmen. The line helped hold the Gamecocks to just 65 yards rushing last week and is the strength of the entire Rebel defense.
The offensive line needs to win the battle, plain and simple. Smith has got to have time to throw, and Vanderbilt's Warren Norman and Jared Hawkins need to have some running room to take some of the pressure of Smith and the passing game.
They also need to get things together mentally; in the first half against Rice they were out of sync and committed several penalties and other mistakes, including a snap when Smith wasn't looking that stopped a promising drive in its tracks.
We'll see what happens. If the above five things happen though, the Commodores will be celebrating.
Or Vanderbilt could just concentrate on scoring 18 points. Ole Miss has scored 17 each of the last three times the teams have met.