It’s the top of the table showdown between joint leaders Napoli and Milan, as Victor Osimhen and Lorenzo Insigne take on Olivier Giroud and Rafael Leao, with Stanislav Lobotka and Franck Kessie stepping in.
It kicks off at the Stadio Diego Armando Maradona at 19.45 GMT.
You can follow all the build-up and action as it happens on the LIVEBLOG.
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These sides went into the round together in top spot, with Napoli ahead on goal difference, but it will be head-to-head record that ultimately decides position.
Inter, who still have a game in hand, also leapfrogged them both by thrashing Salernitana 5-0 on Friday evening.
Hirving Lozano is back in training, so only Kevin Malcuit and Axel Tuanzebe are still out for Napoli, fresh from a last-gasp 2-1 win away to Maurizio Sarri’s Lazio.
Insigne, Piotr Zielinski and Matteo Politano fan out behind Victor Osimhen, with Stanislav Lobotka returning to midfield after his injury lay-off alongside Fabian Ruiz.
Milan have slowed down considerably in recent weeks and played a 0-0 Coppa Italia semi-final draw with Inter midweek.
Alessio Romagnoli picked up an injury, joining Simon Kjaer in the stands, but Zlatan Ibrahimovic is on the bench for the first time in over two months.
That means Giroud and Leao lead the way again, with Franck Kessie in a more advanced role next to Junior Messias.
Ismael Bennacer returns from suspension in midfield.
Napoli have won their last two Serie A meetings with Milan 1-0, but both of those were at San Siro, losing here 3-1 in November 2020.
There was famously controversy earlier this season, with Kessie’s last-gasp equaliser disallowed for Giroud’s offside position.
The Rossoneri are unbeaten in Naples since a 3-2 thriller in August 2018, emerging with a 2-2 draw and 3-1 victory.
Napoli: Ospina; Di Lorenzo, Rrahmani, Koulibaly, Mario Rui; Fabian Ruiz, Lobotka; Politano, Zielinski, Insigne; Osimhen
Milan: Maignan; Calabria, Tomori, Kalulu, Theo Hernandez; Tonali, Bennacer; Messias, Kessie, Leao; Giroud
Napoli win or draw would be perfect