Both teams go into the encounter at the Stadio Olimpico having suffered a drop in form in 2011.
Roma bounced back from a 2-1 defeat to Sampdoria with a 1-0 victory at Cesena on Sunday, courtesy of a late own goal from defender Maximiliano Pellegrino.
Lazio, meanwhile, recorded their first win of the year against Sampdoria at the weekend thanks to a last-gasp goal from substitute Libor Kozak.
The result lifted Lazio into joint-second place in Serie A - level on 37 points with Napoli and two points clear of Roma, who are in fourth.
"We are not giving up on anything this season and especially when it is a derby and the Coppa Italia that we have won nine times," said Roma coach Claudio Ranieri.
Roma, who are without suspended captain Francesco Totti, will play with Jeremy Menez in support of attacking pair Mirko Vucinic and Marco Borriello.
Lazio coach Edy Reja is likely to name an unchanged team with respect to the team that beat Samp, with the Biancoceleste still without injured striker Tommaso Rocchi.
The winner of Wednesday's showdown in Rome will meet Juventus in the last eight of the competition.
Napoli will have to overcome the absence of injured defender Gianluca Grava when they welcome Bologna to the San Paolo stadium tomorrow.
Grava tore a ligament in his left knee during Sunday's goaless draw against Fiorentina and will be sidelined for the rest of the season.
Victory on Tuesday would see Napoli face holders Inter Milan in the quarter finals of the competition.
Inter, who thrashed Bologna 4-1 in Serie A on Saturday, saw off Genoa 3-2 to reach the last eight of the competition.
Udinese take on Sampdoria on Wednesday looking to make it two wins in a row in Genoa.
The Friuli outfit goes into its midweek clash on the back of a 4-2 triumph over Genoa at the Luigi Ferraris stadium. The win lifted the Bianconeri to eighth in the standings.
Rock-bottom Bari will face a mighty challenge when they travel to the San Siro to take on Serie A leaders AC Milan on Thursday.
Bari have clinched just one win in their last 15 league games and last weekend's 2-1 defeat to Juventus was their 12th loss of the campaign.
Massimiliano Allegri's Milan expect to return to winning ways having drawn their last two league games, including Sunday's 1-1 draw at Lecce.
The result left the Rossoneri four points clear at the top of Serie A.