Liverpool will aim to make it six wins from six in the 2021-22 Champions League when they pay a visit to San Siro to lock horns with AC Milan on Tuesday night.
Jurgen Klopp's dominant crop are already assured of their place in the last 16, while the Rossoneri are involved in a three-way battle for second place in Group B.
An inexperienced Liverpool side playing on the San Siro turf for the first time may just come up short this week, especially with Pioli's side having much more to fight for in midweek.
Very rarely are the Reds kept at bay no matter who leads the line, but the Rossoneri's settled XI can follow up their hard-fought Wanda Metropolitano win with a victory that may or may not be enough for a spot in the knockout rounds.
Amid a downward spiral in Serie A, AC Milan travelled to the Wanda Metropolitano to face Atletico Madrid on the penultimate matchday in Group B aiming to avoid being on the wrong end of another 97th-minute Luis Suarez penalty.
Asserting their dominance on the continental stage has not gone at all to plan for the Rossoneri, but in one of the tournament's heart-warming success stories, former delivery driver Junior Messias scored his first goal for the club on his first Champions League start to hand Milan a crucial 1-0 win.
That victory represents Milan's only win of the 2021-22 tournament so far - having lost three and drawn one of their opening four games in Group B - and after seemingly being down and out, the third-placed Rossoneri are now just one point behind second-placed Porto.
Their fate is out of their own hands, but victory at San Siro coupled with a Porto-Atletico stalemate would see Stefano Pioli's men book their place in the last-16, and they have secured back-to-back Serie A wins over Genoa and Salernitana ahead of this battle.
No visiting team has been able to keep a clean sheet on the San Siro turf this season, and there would be no better time for Milan to claim their first Champions League home win since September 2013, especially with Liverpool simply playing for pride.
There would be no repeat of the goal-laden Estadio do Dragao performances of the past for Liverpool on matchday five, as an altered Reds outfit welcomed Porto to Anfield having booked their spots in the knockout stages as expected.
However, the Reds still produced a professional performance to claim a 2-0 win and maintain their 100% record in Group B, as Thiago Alcantara scored a peach of a strike before Mohamed Salah came up with his customary goal.
Only Ajax and Bayern Munich can also boast a perfect record of five wins from five ahead of the final matchweek, but upon their return to domestic action, the Reds were bailed out by last-minute hero Divock Origi in the last knockings of a hard-fought 1-0 win over Wolverhampton Wanderers.
That narrow win marked the end of the Reds' astonishing two-goals-per-game streak - which stood at 18 matches before the trip to Molineux - but they have now won five on the bounce in all tournaments and boast eight goals from their two away games in Group B so far.
Liverpool came up trumps in a 3-2 thriller with AC Milan during September's battle at Anfield, but the 2005 and 2007 finalists have never locked horns at the inimitable San Siro before.
Milan's attacking forces have taken quite the hit in recent weeks, with Olivier Giroud, Samu Castillejo and Ante Rebic being joined in the medical bay by Pietro Pellegri, who came off after 15 minutes against Salernitana on Saturday with a groin issue.
Zlatan Ibrahimovic is therefore sure to lead the line after being rested at the weekend, but Davide Calabria remains out and Simon Kjaer will miss several months with a devastating ACL injury.
Mike Maignan's recent return is a huge boost, though, and Messias's heroics against Atletico may not be enough to see him edge out Brahim Diaz for this crucial battle.
Rafael Leao is also reportedly set to miss out after taking a blow to the thigh at the weekend, so Rade Krunic could be in line for a start on the left.
As for Liverpool, Joe Gomez and Naby Keita are back in training and could potentially return in midweek, but Roberto Firmino, Curtis Jones, Harvey Elliott and the suspended James Milner are all unavailable.
Gomez and Keita will surely not be risked from the off with nothing on the line, but there should be opportunities for Tyler Morton and Alex Oxlade-Chamberlain to start in the middle as Thiago Alcantara enjoys a rest.
Ibrahima Konate, Kostas Tsimikas, Neco Williams and Takumi Minamino could also be rotated into the XI, and it would not be a surprise to see Origi - who Klopp joked he would 'write a book about' - lead the line.
AC Milan possible starting lineup:
Maignan; Kalulu, Tomori, Romagnoli, Hernandez; Kessie, Tonali; Saelemaekers, Diaz, Krunic; Ibrahimovic
Liverpool possible starting lineup:
Alisson; Williams, Konate, Van Dijk, Tsimikas; Morton, Henderson, Oxlade-Chamberlain; Salah, Origi, Minamino