However, with just 10 games left to play only three points separate them in the Serie A table as a mid-table finish beckons for each club.
While Milan started the season with aspirations of qualifying for Europe, it was a very different story for a Palermo side marking their return to Serie A.
The Rosanero were heavily expected to be in a battle against relegation and in the early weeks of the season it was certainly appearing that way, as they did not win any of their opening six league games.
They finally broke that duck with a 2-1 victory over Cesena to lift them off the bottom of the table and they haven't looked back since.
An unbeaten run throughout November and December followed and although their form has trailed off since the turn of the year, they are 14 points clear of the bottom three and their top-flight status looks secure.
The form of attacking duo Paulo Dybala and Franco Vazquez has also been highlighted as one of the reasons for Palermo's success, but they have struggled in recent weeks, with their club unable to find the net in their previous four league games.
Recent form: WLDDLL
It has been another turbulent campaign for Milan, who have struggled to emulate the great teams that have come before them in their illustrious history.
That early optimism was quickly wiped out and a number of under-par displays have led to intense speculation surrounding Inzaghi's future beyond the end of May.
The Rossoneri have won just nine of their 28 league matches this season and currently sit nine points away from the final European spot.
A late bid for a top-five finish looks well beyond their reach, given that their only victories in 2015 have come against the three clubs in the relegation zone.
Recent form: DWDDLW
The absence of the two defenders could force manager Giuseppe Iachini into a reshuffle at the back, but further up the pitch Dybala and Vazquez are expected to lead the attack.
Palermo possible starting lineup:
Sorrentino, Vitiello, Gonzalez, Terzi, Daprela, Barreto, Maresca, Rigoni, Quaison, Vazquez, Dybala
Milan possible starting lineup:
Lopez, Abate, Mexes, Paletta, Antonelli, Poli, De Jong, Bonaventura, Honda, Menez, Destro
Head To Head
Palermo pulled off one of the shocks of the season when these teams last met, as an own goal from Zapata and a strike from Dybala saw them earn a 2-0 win over Milan at San Siro.
There has been plenty of excitement whenever they have played each other and there have been 31 goals scored in their past 10 meetings.
We say: Palermo 2-2 AC Milan
Palermo and Milan are both struggling for form, but they are both more than capable of finding the back of the net. Due to the attacking players on show and the defensive frailties of each team, there could be plenty of goals, so we think that the match will end in a high-scoring draw.