Edy Reja's men have been in good form of late, losing just two of their last 11 league games - a run that has lifted them to seventh in the table, six points behind Inter and a Europa League berth.
Lazio have qualified for Europe's secondary competition in each of the past three seasons, and they need to put a strong run of results together over the final 10 games of the season if they are to continue that trend.
The capital club will take comfort from having home advantage against Clarence Seedorf's struggling side, as they have already beaten Inter and drawn with top two Juventus and Roma at the Stadio Olimpico this term, although they lost 1-0 to Atalanta in their last home outing.
Michael Ciani's equaliser earned Lazio a 1-1 draw in the reverse fixture at San Siro back in October, and although Milan have had a change of manager since then, their fortunes have scarcely improved.
Club legend Seedorf took over from Massimiliano Allegri in January and after an initial mini-resurgence under the Dutchman, the 18-time Italian champions have fallen away again.
Milan, who sit 11th in the table, have lost five of their last six in all competitions, including a 4-1 thumping by Atletico Madrid in their UEFA Champions League last-16 second leg that completed a 5-1 aggregate victory for the Spaniards.
It has been a turbulent season at San Siro, with the club looking destined for a mid-table finish that would see them miss out on European football for the first time since their 10th-placed finish in the 1997-98 campaign.
They responded in style to win the Scudetto 12 months later, but it will take a huge turnaround to repeat that next season with Juve - who look set to win a third title in a row this season - looking back to their imperious best.
Milan goalkeeper Christian Abbiati is suspended for the trip to Rome after his early red card in the 4-2 home defeat to Parma last time out.
He is likely to be replaced by Marco Amelia, while for Lazio, keeper Federico Marchetti (flu) is a doubt and striker Helder Postiga, yet to feature since arriving on loan from Valencia in January, continues to struggle with a back problem.
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