Lazio will look to reverse recent history as they go in search of their first Serie A win at San Siro against Milan since 1989.
Wednesday's clash will give both sides – who are two of the biggest clubs in Italian football – a chance to revive their season after making slow starts.
Lazio – who last won a league game against Milan at the venue in September 1989 thanks to Paolo Maldini's own goal - have struggled recently, winning just one of their last six matches in all competitions.
After winning three of their first five Serie A fixtures, they have fallen to seventh in the table, with a lack of goals a concern for manager Vladimir Petkovic.
The Rome club have scored 14 goals in nine matches this season – only one side in the top half of the table has scored less – with only midfielder Antonio Candreva having netted more than two league goals, he has four to his name.
Lazio winger Senad Lulic (thigh) will not feature in the clash, while defenders Andre Dias (knee) and Vinicius (hamstring) will also miss out.
Milan will be hopeful a return to San Siro inspires them to victory after they fell to 10th in the table following a 3-2 defeat at Parma on Sunday.
Massimiliano Allegri's side are already 16 points adrift of table-toppers Roma and, despite the season still being in the opening quarter, a 19th Scudetto looks beyond them.
Their abysmal away form is largely to blame, with Sunday's loss just the latest in a string of disappointing results on the road.
Milan have won none of their five away matches this season, losing three and drawing two, while they have conceded 13 goals in the process.
"We keep making the same mistakes away from home," Allegri bemoaned after the loss to Parma.
"Mario Balotelli had a bad game. Now our race to get back near the top is getting tougher."
Milan can take some comfort in their home form, having won three of their four matches at San Siro this season, but they need more from their strikers.
Balotelli, Robinho and Alessandro Matri have scored a combined total of just six goals for a side who are badly missing young star Stephan El Shaarawy (foot) and striker Giampaolo Pazzini (knee).
Defenders Philippe Mexes (suspension), Daniele Bonera (knee) and Matias Silvestre (calf) will also miss the match.
This fixture has not been won by an away side in the last seven meetings, with Milan winning the most recent encounter 3-0 in March thanks to a Pazzini double.
|2||M. De Sciglio||58'|
|34||N. de Jong|
|Coach: M. Allegri|
for V. Birsa 75'
for S. Muntari 75'
for Kaká 84'
|Bruce rues calamitous Huddlestone miss|
|UEFA Europa League Review: Torino mark return with big win, Lyon victorious|
|Southampton win again|
|Jenkinson agrees West Ham loan|
|Tottenham agree Dier move|
|Rincon seals Genoa move|
|Dunne announces international retirement|
|Romulo close to Juve switch|
|Trencin 0 Hull City 0: Huddlestone pays penalty in Hull stalemate|
|Rennes prise Prcic away from Sochaux|
|CSL Preview: Liaoning look for swift response, buoyant R&F visit Henan|
|Pique desperate to regain high standards|
|Marseille agree three-year Stade Velodrome lease|
|Torres will not be leaving, says Mourinho|
|Bastia bring in Brandao|
|Paris Saint-Germain v Guingamp: League and cup winners battle for Trophee des Champions|
|Argentine Primera Division suspended after Grondona death|
|Immobile: Lewandowski is the past, I am the future|
|Rose pens new Tottenham deal|
|CSL Review: Evergrande end Harbin run, Henan edge clear of danger|
|Ivory Coast appoint Renard|
|Three-man shortlist for South Korea post|
|MLS Preview: Sounders aiming to bounce back against Earthquakes|
|Personal reasons behind Evra´s Juve switch|
|Liga MX Preview: Monterrey out to continue winning run|
|J.League Preview: Oenoki begins S-Pulse reign at Tokyo|
|K.League Preview: Jeonbuk face tricky Jeonnam test, Pohang visit Suwon|
|Kakuta loaned to Vallecano|
|Morrison remanded in custody|
|Hernandez coy on United exit|
|Neymar on road to recovery|
|Feyenoord capture Wilkshire and Basacikoglu|
|Yoel makes Valencia switch|
|Heaton extends Burnley deal|
|Lees leaves Leeds for Wednesday|
|Caballero eyes first-team action|
|Newcastle ´monitoring´ Remy, claims Pardew|
|Rodriguez ready to fight for Real place|
|Cavani ´certain´ he will stay with PSG|
|Morrison charged with assaults|
|Copenhagen slam security after fan violence in Kiev|
|Gerrard: Suarez ´too good´ for Arsenal|
|Mourinho explains Lukaku exit|
|Simeone content with Atleti workout|
|Milligan: Australia targeting Asian Cup|
|Ronaldinho rules out retirement|
|Rodgers challenges Henderson|
|Jovetic can be City catalyst - Pellegrini|
|Janko joins Sydney as marquee|
|Deila ´unbelievably disappointed´ with Celtic|
|MLS Review: DC close on Sporting, Red Bulls hold RSL|
|Ecuadorian Primera A Review: Emelec crowned champions|
|Bolivar 1 San Lorenzo 0 (agg 1-5): Visitors advance to maiden Libertadores final|
|Gerrard open to move abroad|
|Lukaku tells Chelsea ´no hard feelings´|
|Zaha eager to impress Van Gaal|
|Liverpool down Man City after shoot-out|
|Atletico fall to Gonzalez´s penalty heroics|
|Glazers offer up 8m United shares|
|Bertrand joins Southampton on loan|
|Van Aanholt features as Sunderland fall to defeat|
|UEFA Champions League Review: Celtic hammered in Warsaw|
|Collison stakes his claim as QPR are held|
|Newcastle youngsters edge to Wednesday win|
|Villa beaten by buoyant Chesterfield|
|Juve held by new boys Cesena|
|Late Drinkwater strike helps Leicester see off Walsall|
|Everton seal club-record Lukaku deal|
|Lazio complete De Vrij capture|
|Fabregas opens account in Chelsea win|
|AFA president Grondona dies aged 82|
|Trezeguet heading for Indian Super League|
|Premier League to introduce vanishing foam|
|Rennes bring in Bruls|
|Kehl steps down as Dortmund captain|
|Capello: I´m staying until 2018|
|Pedro saddened by Fabregas departure|
|Fernandez agrees Porto switch|
|West Ham close on Jenkinson, says Allardyce|
|Donnelly out for three months|
|Chambers: It has been a whirlwind|
|Lukaku drops Chelsea exit hint|
|Mee signs new deal at Burnley|
|Lovren denied United States visa|
|Redknapp admits Fer interest|
|No official Cuadrado bids, insists agent|
|Maguire ready to make step up|
|Rodgers: Liverpool have a strategy in transfer market|
|Ki out to prove himself at Swansea|
|Garcia plays down importance of Real scalp|
|Evian complete Bruno signing|
|Poyet frustrated by lack of new faces|
|Mexes convinced Milan are improving|
|Mazzarri praises Inter attitude|
|Ronaldo could face Manchester United - Ancelotti|
|Tevez thanks fans after father found ´safe and well´|
|Gabi braced to tackle big-spending rivals|
|Shaw: I deserved Van Gaal criticism|
|Morinigo surprised by Gedoz substitution|
|Honduras appoint Medford|
|Van Gaal delighted with United display|
|Roma battle past Real Madrid|
|Simeone talks up Hernandez transfer|
|Defensor Sporting 1 Nacional Asuncion 0 (1-2 agg): Visitors into final despite loss|
|United edge Inter on penalties|
|Gerrard: It´s been ´the worst three months of my life´|
|Sabella set to quit Argentina post|
|Toure plans to see out career with City|
|Tevez´s father released after kidnapping|