The home side are currently second in the table, four points behind leaders Juventus, while Milan sit seventh, two points behind sixth-placed Napoli, who have a game in hand.
Lazio have not won Serie A since the 1999-2000 season, while they have not even made the top four since 2014-15, finishing eighth, fifth, fifth and eighth in their last four campaigns at this level.
The Rome giants have been in terrific form this term, though, winning 21 of their 29 league games, suffering just three defeats in the process, to occupy second position in the table.
Lazio are only four points behind leaders Juve on the same number of matches, although the Old Lady will have the chance to move seven points clear before this particular game kicks off on Saturday night.
Only a win will do for Simone Inzaghi's side as they chase down the champions, and they will enter the match off the back of successive 2-1 victories over Fiorentina and Torino.
I Biancocelesti actually lost 3-2 to Atalanta BC on their return to action on June 24, but they have been in excellent form on home soil this term, winning 12 of their 15 games, remaining unbeaten in the process.
Milan, meanwhile, have been in strong form since returning to action after the lockdown period, picking up seven points from an available nine to boost their top-six hopes.
The Italian giants were held to a 2-2 draw at SPAL on Wednesday night, but they had beaten Lecce and Roma in their two matches between June 22 and June 28 as the Serie A season resumed.
Stefano Pioli's side are currently seventh in the table on 43 points, two points behind sixth-placed Napoli, who are in action away to Atalanta on Thursday night.
Fifth-placed Roma are just five points ahead of Milan, meanwhile, and the Red and Blacks will be hoping that both teams directly above them drop points before this weekend's contest.
Lazio recorded a 2-1 victory in the reverse match at San Siro earlier this season, but Milan picked up a point when they last visited the Rome giants back in November 2018.
Lazio Serie A form: WWWLWW
Milan Serie A form: WDLWWD
Milan form (all competitions): DLDWWD
Lazio will be without both their leading scorer Ciro Immobile, who has scored 32 times this season, and fellow attacker Felipe Caicedo this weekend due to the yellow cards that the pair picked up against Torino on Tuesday night.
Joaquin Correa is expected to feature in the final third due to the absences of Immobile and Caicedo, while Luis Alberto could be pushed further forward, possibly opening the door for Andre Anderson to feature in midfield.
There are not expected to be many changes from the side that started against SPAL on Wednesday night, meaning that Ante Rebic should again lead the line.
Lazio possible starting lineup:
Strakosha; Patric, Acerbi, Radu; Lazzari, Milinkovic-Savic, Parolo, Anderson, Jony; Alberto; Correa
Milan possible starting lineup:
Donnarumma; Calabria, Gabbia, Romagnoli, Hernandez; Kessie, Bennacer; Castillejo, Paqueta, Calhanoglu; Rebic
We say: Lazio 2-1 AC Milan
The fact that Lazio are missing their leading scorer is a huge boost for Milan, who will be determined to record their 13th league victory of the season. It would not be a surprise to see the two sides share the points, but we just fancy Lazio to sneak a victory despite their absentees.