While the home side currently sit in 17th position in Serie A, Lecce are third in the second tier after seeing their long unbeaten run ended at the weekend.
As they contend with their most difficult period of the season, Spezia boss Thiago Motta may welcome the opportunity to turn his attention to the cup this midweek.
A run of four defeats in five games - the latest coming away at Roma on Monday - has left Spezia just two points above the relegation zone with a trip to Napoli still to come before Christmas.
While they had their moments against Atalanta BC and Sassuolo, Aquilotti failed to build on their advantage on both occasions, and there is a feeling that a winnable tie in the Coppa Italia has come at the right time.
Spezia can take pride from their home record this season, their only defeat in five matches being due to a late penalty from Bologna on November 28.
Motta's side reached this stage of the competition with a 3-1 victory away at Serie B strugglers Pordenone back in August.
As far as Lecce are concerned, they have been one of the more impressive teams in the second tier this season, I Giallorossi collecting 31 points from their 17 matches.
Nevertheless, a 15-match unbeaten streak came to an end on Saturday as they succumbed to a 1-0 defeat at leaders Pisa, leaving them four points off the pace.
Marco Baroni's side earned their spot in this round of the competition with a terrific 3-1 triumph at Parma during the middle of August.
Having lasted just 17 minutes against Roma, Jacopo Sala is expected to miss out in the Spezia midfield.
Goalkeeper Jeroen Zoet will also hope to return between the sticks having not featured since October 3.
While Baroni's focus is promotion back to the top tier, the Lecce boss may keep changes to a minimum.
Spezia possible starting lineup:
Zoet; Amian, Erlic, Hristov; Ferrer, Kovalenko, Maggiore, Verde, Reca; Manaj, Strelec
Lecce possible starting lineup:
Gabriel; Gendrey, Dermaku, Bjarnason, Barreca; Gargiulo, Blin, Majer; Listkowski, Olivieri, Di Mariano
We say: Spezia 2-1 Lecce
Despite these two teams being a league apart, we expect an evenly-matched contest to play out on Thursday. While Lecce will fancy their chances of edging this contest, Spezia may just have enough in the tank to prevail by the odd goal in three.
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