With the home side participating in the second tier and the visitors bottom of the Eredivisie, this is an opportunity for both teams to stay in the hunt for a surprise place in the final.
Match preview
Sitting down in eighth position in the Eerste Divisie standings, Cambuur's priority is moving up the table to try to earn a return to the top flight.
However, their recent form has been poor, with just one win being posted in their last five fixtures in the second tier.
Nevertheless, they did earn a 1-1 draw away at leaders Willem II in their most recent outing, providing Henk de Jong and his players with a boost ahead of this contest.
The Yellow-Blues have managed to reach this stage of the competition without encountering a top-flight side, impressively scoring 11 times in just three ties.
That said, it took a remarkable comeback to overcome USV Heracles in the previous round, Cambuur having been trailing with 11 minutes to go before going on to prevail 4-3 after extra time.
As far as Vitesse are concerned, this is a welcome distraction from what has been a disastrous Eredivisie campaign, just 12 points coming from their 20 matches.
Vitesse sit seven points adrift of 15th position, currently making a relegation playoff spot their most realistic best-case scenario, but Edward Sturing will take positives from their most recent games.
Just five goals were shipped in the triple-header of Feyenoord, PEC Zwolle and Go Ahead Eagles, while a clean sheet was kept in a goalless draw with FC Utrecht preceding those games.
A 1-0 triumph over Heerenveen has been posted in this competition, either side of victories over Groene Star and AFC by the same scoreline.
Cambuur KNVB Beker form:
Cambuur form (all competitions):
W
L
W
W
L
D
Vitesse KNVB Beker form:
Vitesse form (all competitions):
W
D
W
L
L
L
Team News
De Jong could be prepared to name the same Cambuur side that held Willem II on Friday evening.
If he wants to bring a more defensive-minded option into the team on the flank, Tyrique Mercera could replace Agustin Anello.
Young forward Milan Smit has netted three times in this competition, while 15 goals have also been scored in the league.
With Marco van Ginkel being withdrawn after just 26 minutes against Go Ahead Eagles, Vitesse boss Sturing is expected to recall Kacper Kozlowski.
Having recently joined on loan, Anis Hadj Moussa may also be provided with a start on the right wing.
Cambuur possible starting lineup:
Van Osch; Tol, Smand, Bergsma, Poll; Van Mullem, Breij; Balk, De Jong, Anello; Smit
Vitesse possible starting lineup:
Room; Arcus, Isimat-Mirin, Hendriks, Pinto; Domgjoni, Cornelisse; Hadj Moussa, Kozlowski, Boutrah; Meerdink
We say: Cambuur 0-1 Vitesse
Both teams will feel that they deserve to be favourites for this contest, and we can see the value in backing a win for the second-tier side. However, Vitesse have improved defensively of late, leading us to predict a hard-fought win for the Eredivisie team.