Last season's thrilling final win over city rivals Roma was the undoubted highlight of Vladimir Petkovic's reign at the club - the coach was sacked last week after agreeing a move to Switzerland's national team in July.
Edy Reja's subsequent return to the Stadio Olimpico has produced mixed results thus far, with Saturday's frustrating 0-0 draw at Bologna following a 1-0 win over Inter on home soil.
The Rome outfit have won four of their last five home games against Parma, the Emilia-Romagna club last beating Lazio 3-1 in March 2012, a result sealed by Sergio Floccari's double, who was on loan from the capital at the time.
Floccari remains a Lazio player and will be eyeing a goal, having failed to find the net in 13 Serie A games so far this term.
Parma head into the contest in good form, having avoided defeat for nine games - a run stretching back to November 2, when they lost to Serie A table-toppers Juventus - and a 3-0 weekend win over struggling Livorno will have boosted confidence even further in Roberto Donadoni's squad.
Milan host second-tier Spezia and may be looking to use the competition as a distraction to their dismal Serie A campaign this season that sees them sit 11th after 19 games.
Sunday's 4-3 defeat at Sassuolo was one of the worst results in the club's history and the Coppa Italia may be their only hope of salvation this term.
After winning the competition five times between 1967 and 1977, the San Siro giants have been triumphant just once more, in 2003.
Massimiliano Allegri will leave Milan at the end of the season and cup success would end his topsy-turvy spell with the club on a high.
January recruits Adil Rami and Keisuke Honda may be in line to make their first starts for the club, with the latter having come off the bench on Sunday while the former was unused.
The tie will represent Spezia's first outing since Serie B's mid-season break and they will have been stewing over the festive period after a 4-1 defeat to Latina before the new year.
Napoli, winners of the competition in 2012, will be confident of sealing a spot in their home tie against Atalanta - who have lost all but two of their away games this term.
The sides met at Stadio San Paolo in August - Rafael Benitez's men sealing a 2-0 win courtesy of goals from Gonzalo Higuain and Jose Callejon.
In Wednesday's other tie, Serie B's Siena will target an upset when they travel to top-flight strugglers Catania.
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