The ever-fiesty Gattuso welcomes his old club to San Paolo, as he takes part in a most likely unsentimental reunion with Daniele Bonera. His former Milan and Italy teammate will be in temporary charge of the Rossoneri owing to the absence of both Pioli and his assistant Giacomo Murelli.
Napoli are unbeaten in their last 11 encounters against Milan in Serie A - winning six of those - and are in fact the last side to stay unbeaten versus the Rossoneri in the top-flight for a sequence of 12 or more games - between 1974 and 1979.
If they are to match that record run, the Partenopei will have to shatter Milan's impressive unbeaten away record. Sunday's visitors are unbeaten in their last 14 games away from home in all competitions, winning nine, and the last time the Rossoneri enjoyed a longer run was for a total of 15 matches - under the expert guidance of Carlo Ancelotti, back in 2004.
In recent history, though, Milan have rarely fared well after the long journey south to Naples, having won just one of their 14 Serie A away encounters with Napoli in the 21st century, losing seven.
Precedent has been pushed aside time and time again by their Pioli-lead resurgence, so the 18-time Scudetto winners will not be deterred as they take on one of their toughest tests yet - with one Swedish superstar in particular sure to cause some serious consternation.
Milan's irrepressible striker Zlatan Ibrahimovic has netted in each of his first five Serie A games this season and in the three-points-per-win era only three players have managed to score in their first six appearances of a campaign - Gabriel Batistuta in 1994-95, Christian Vieri in 2002-03 and ex-Milan striker Krzysztof Piatek during his explosive 2018-19 campaign with Genoa.
Just before the international break, Milan endured a bumpy ride against Verona, but ultimately Zlatan once more saved the day, bringing his domestic tally to eight goals and sealing a two-all draw.
Both Ibrahimovic, 39, and Gattuso - three years his senior - played together at Milan when the club won the last of their 18 titles back in 2011 but there will only be time for sharing warm words after the game. Both have their eyes firmly only on one prize - which is handed out in May - though the Napoli chief claims he does not encourage any talk about the Scudetto, urging his players to "calm down" in pursuit of a first league title since the heady halcyon days of 1990.
Ex-Rangers midfielder Gattuso may be forced into a reshuffle ahead of this vital encounter, as Victor Osimhen, who scored the pivotal goal against Bologna last time out, suffered a shoulder injury on Nigeria duty and is unlikely to feature. With more diminutive stars Piotr Zielinski, Eljif Elmas and Dries Mertens in pole position to take on the attacking impetus in his stead, the Napoli approach may be more nuanced than usual.
Allied to their substantial forward options, the Partenopei have only let in four goals on the field of play - with a further three conceded in the courtroom, following a controversial ruling that their cancelled fixture with Juventus should be awarded 3-0 to the Bianconeri.
Therefore, Milan's task in holding off the hordes gathering behind them in the Serie A table will be made all the more challenging on Sunday.
Napoli Serie A form: WLWWLW
Napoli form (all competitions): LWWLWW
AC Milan Serie A form: WWWDWD
AC Milan form (all competitions): WDWWLD
Napoli's record signing Victor Osimhen incurred a shoulder injury during the international break and will be replaced by a very different central striking option in Dries Mertens. If a more conventional number nine is required, Andrea Petagna is also poised to deputise.
Causing Gattuso some rare defensive concerns, both Amir Rrahmani - of Kosovo - and Albania's Elseid Hysaj returned from international duty having tested positive for COVID-19. The back four should therefore comprise Giovanni Di Lorenzo and Mario Rui on the flanks and trusted pair Kalidou Koulibaly and Kostas Manolas in the centre. Goalkeeper David Ospina returns to the bench.
For Milan, in-form Rafael Leao is the only player definitely unavailable, due to a thigh injury sustained on international duty with Portugal, though defenders Mateo Musacchio and Alessio Romagnoli are also doubtful.
Ante Rebic belatedly returns after an elbow injury sustained in September and will most likely replace Leao on the left of Milan's attacking trio, though Samu Castillejo could also be given the nod in what should otherwise be a familiar and settled Rossoneri XI.
Napoli possible starting lineup:
Meret; Di Lorenzo, Manolas, Koulibaly, Rui; Ruiz, Bakayoko; Lozano, Politano, Insigne; Mertens
AC Milan possible starting lineup:
Donnarumma; Calabria, Kjaer, Romagnoli, Hernandez; Kessie, Bennacer; Saelemaekers, Calhanoglu, Rebic; Ibrahimovic
We say: Napoli 2-2 AC Milan
Just the sort of big-time clash needed to relaunch Sunday night Serie A after the international break and expectations are sky-high for an entertaining encounter in Naples.
Both sides boast an array of attacking talents - though Rafael Leao and Victor Osimhen unfortunately miss out - so the most probable outcome is a score draw, which either side would be happy to take - even if they would not freely admit it.