With both of last season's finalists, Ajax and PSV Eindhoven, out of the competition, and Feyenoord facing AZ Alkmaar this week, the cup is wide open heading into the last eight.
Match preview
While currently competing in the Eerste Divisie, Groningen can take confidence from the fact they are one of the most in-form sides in Holland at present.
A defeat to Dordrecht at the weekend was a slight low point, but that was their first defeat in 14 games.
Dick Lukkien's side are likely to claim a playoff place as they look to make an instant return to the top flight, as their tally of 23 is more than any other side has taken in the second tier over the past 10 games.
Strong league form has complemented their run in the Beker too, as all three rounds so far have seen them win away from home - including against Eerste Divisie leaders Willem II and top-flight Excelsior.
Groningen now have an excellent chance to reach just a third semi-final in almost four decades, while there will be faint belief they could repeat the feat of winning the competition as they did in 2015.
Sittard cannot match Groningen's achievements in this competition in recent times, as their last success came in 1964, and they have only progressed past the quarter-finals once in 40 years.
However, they have the upper hand in recent meetings, as they completed the double over their upcoming opponents when Groningen were relegated from the Eredivisie last season.
Sittard also enter the fixture unbeaten in their last four away games, winning three, two of which came in the cup.
Like Groningen, Sittard have come through three rounds, winning each away from home, with Kaj Sierhuis proving crucial with three goals in their previous two cup ties.
That form has been present on the league front too, as Danny Buijs's men are challenging for a spot in the Europa Conference League playoffs, as relegation fears were put to bed a long time ago.
Groningen KNVB Beker form:
Groningen form (all competitions):
W
W
W
W
W
L
Fortuna Sittard KNVB Beker form:
Fortuna Sittard form (all competitions):
W
L
W
D
W
D
Team News
Groningen allowed striker Kevin van Veen to return to Scottish football late in the January window, so will look to youngster Romano Postema for inspiration in attack.
The attacker has been crucial in their run through this competition, scoring in the 3-1 win at Willem II, as well as notching both in their impressive victory at Excelsior.
With a fully fit squad at Lukkien's disposal, that could see Rui Mendes remain on the bench as he waits for a first start since moving from Emmen.
Sittard's only absentee in the past few weeks is available again as Deroy Duarte has returned from the Africa Cup of Nations after Cape Verde's elimination.
Michael Verrips is set to start in goal despite being a Groningen player just a month ago, as the sale of Ivor Pandur to Hull City means Sittard have recalled the stopper and implemented him as number one.
Alen Halilovic is the man in form after two goals against Heerenveen, and he is set to start alongside Justin Lonwijk in midfield after he was signed to replace the outgoing Tijjani Noslin last month.
Groningen possible starting lineup:
Jurjus; Bacuna, Rente, Bakker, Prins; Schreuders, Pelupessy, Hove, Valente; Van Bergen, Postema
Fortuna Sittard possible starting lineup:
Verrips; Ivo Pinto, Guth, Siovas, Dijks; Halilovic, Rosier, Lonwijk; Inigo Cordoba, Sierhuis, Peterson
We say: Groningen 1-2 Fortuna Sittard
Both sides are in good form, and it is set to be an intriguing cup tie between two clubs who would not have been fancied to get far before a ball was kicked in the competition.