The past four encounters have been in the final of the much-maligned competition, but this time the pair clash in the quarter-finals at a pivotal moment of the season for Inter.
The Serie A champions lost their second league game this term on Sunday when they were humbled 3-1 at Atalanta having also dropped points the weekend before in the 1-1 home draw with Cagliari.
Juventus now lie just three points behind Jose Mourinho's side in the league and although the Italian Cup is Inter's third priority this season, a good performance against Roma is needed to prove their struggles are just a blip.
"It is the perfect opportunity to rediscover our morale straight away," Inter captain Javier Zanetti told reporters.
The one-leg match at the San Siro has taken on such an importance that Inter's main striker Zlatan Ibrahimovic may start given he is suspended for next weekend's league match against Sampdoria.
The Swede would usually be rested for a cup game.
Roma, still without the injured Francesco Totti, will hope stand-in striker Julio Baptista continues his good form after scoring three goals in two games.
Udinese, who have not won in 10 matches in Serie A, will hope for some respite in their home quarter-final match with fellow strugglers Sampdoria on Wednesday while Lazio host faltering Torino on Thursday.
The final quarter-final between Juventus and Napoli in Turin takes place on February 4.
