In the season's second Derby della Capitale, there will have to be a winner, after the sides shared the spoils in a drab 0-0 draw back in November.
Match preview
Lazio continue to be one of the most in-form sides in Italy, as their last 12 league games have now yielded an impressive 23 points.
That comes after a third straight win was secured at the weekend, as Matias Vecino's late strike earned Lazio a 2-1 victory at Udinese.
That saw Lazio pick up where they left off to start 2024, after Maurizio Sarri's side signed off for 2023 with two wins over Empoli and Frosinone.
After spending most of the early stages of the season near the bottom, Lazio's form now finds them just three points shy of the top four.
It was important for the Biancocelesti to continue their fine run given the string of huge encounters they have coming up, starting with the derby, and followed by their Supercoppa semi-final against Inter Milan next week.
Napoli and Atalanta BC are also on the horizon for Sarri's men, in two games that will be pivotal in the race for the top four.
While it provides an opportunity for one of the clubs from the capital to claim bragging rights over the other, Sarri has voiced his displeasure over the scheduling of the Coppa though.
Speaking after the weekend's win, Sarri said: "I don't like the Coppa formula, everyone knows that. By now, we are not even interested in our passage to the next round, but only to win the derby for our people."
Lazio are a club with great pedigree in this competition, especially recently, as they have won it on five separate occasions in the 21st century alone.
However, since the departure of former manager Simone Inzaghi in 2019 after winning the competition, they have gone out at the quarter-final stage in each season.
The hosts do bring good recent form in the derby into this encounter though, after doing the double over Roma last season.
An extremely dull and disappointing 0-0 draw earlier this season means Roma have still not won a single derby as the designated away team since 2016.
Jose Mourinho had another eventful night in the Roma dugout on Sunday, after the Giallorossi drew 1-1 with Atalanta here in the capital.
Roma fell behind through Teun Koopmeiners's strike, before Paulo Dybala equalised from the spot, as Mourinho would go on to be booked and then given a straight red card for dissent.
Having now fallen behind Lazio in the league table, Mourinho then opted to snub his media duties following the game, as Roma sit eighth in Serie A.
Just one win in five league games is concerning for the Roma faithful, and they will agree they were slightly fortunate to edge past Cremonese 2-1 in the last 16 just a week ago.
Lazio's quarter-final record might be poor, but Roma's is even worse, as they have failed to get beyond this stage since the 2016-17 season.
While a 10-year spell between 2003 and 2013 saw Roma reach seven finals, winning two in 2007 and 2008, that form has evaded them in recent years.
Lazio Coppa Italia form:
W
Lazio form (all competitions):
D
L
L
W
W
W
Roma Coppa Italia form:
W
Roma form (all competitions):
W
L
W
L
W
D
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Team News
Lazio are set to remain without captain and leading goalscorer Ciro Immobile for this clash, as the Italian international has a hamstring injury.
Luis Alberto is also currently absent with a groin strain, and speculation around Felipe Anderson's future could see Sarri opt for Mattia Zaccagni and Gustav Isaksen out wide.
Defensive duo Alessio Romagnoli and Manuel Lazzari returned from injury and suspension, respectively, at the weekend, and while neither started, both could come into the side here.
After being snubbed by the Japan squad for the upcoming Asian Cup, Daichi Kamada started in the win over Udinese and could keep his place in Luis Alberto's absence.
Roma do have two players away on international duty, though, as Algeria's Houssem Aouar and Ivory Coast's Evan N'Dicka are away at the Africa Cup of Nations.
N'Dicka's absence, and the half-time substitution of Diego Llorente on Sunday, gave 18-year-old Dean Huijsen the opportunity to make his debut after joining on loan from Juventus last week.
Mourinho has called the young Dutchman one of the best defensive prospects in Europe and could reward with him a start, despite the magnitude of the occasion here.
On the injury front, Tammy Abraham, Chris Smalling and Renato Sanches all remain out with long-term injuries for the visitors.
Lazio possible starting lineup:
Provedel; Lazzari, Romagnoli, Patric, Hysaj; Guendouzi, Rovella, Kamada; Isaksen, Castellanos, Zaccagni
Roma possible starting lineup:
Svilar; Celik, Kristensen, Mancini, Huijsen, Zalewski; Bove, Cristante, Pellegrini; Dybala, Lukaku
We say: Lazio 1-1 Roma (Lazio to win on penalties)
In a game that could well be relatively cagey and go the distance, Lazio's recent form and results against Roma could give them the edge.