Since it opened in 1926, the San Siro has hosted dozens of famous European Cup nights.
Seven-time winners Milan will be hoping for another one on Wednesday as they welcome a side they have already played four times in the past two seasons: Barcelona.
Despite being billed as underdogs, the Rossoneri are certainly feeling confident: vice-president Adriano Galliani says, via ESPN FC, they have "no psychological weakness towards them," while Mathieu Flamini hopes to exploit his knowledge of Cesc Fabregas and the weaknesses in their squad.
And Milan are also enjoying a rich vein of form. After dipping to 15th in Serie A near the end of 2012, they are undefeated in the league in 2013 and have scored at least two goals in each home match. With owner Silvio Berlusconi on the brink of an unlikely fourth term in office, and his team performing well, spirits are high.
Sadly, high spirits and good form will probably not be enough to overcome this Barcelona side.
In their last four European games at the San Siro, Milan have scored just one goal. They had 58 shots and only converted one of them, an Alexandre Pato effort in the group-stage draw with Malaga (statistic via Yahoo! Eurosport).
In their last five Round of 16 home games, the Italians have managed seven goals. That sounds promising, but they also conceded six valuable away goals in those games.
Furthermore, Barcelona have scored nine times in their last five Round of 16 away trips, and have only failed to score once in all competitions this season (a 0-0 draw at Benfica that was enough to knock the Portuguese side out).
So, there will be goals in this one—there have been an average of 3.25 in their last four meetings—but more of them will probably be scored by the visitors, particularly if Milan continue their recent European form.
They have yet to win a Champions League home match in this campaign, and with just eight points accrued in Group C, they were the poorest performing side to reach the knockout stage.
Barcelona, meanwhile, have been victorious in eight of their last 11 European away games.
Milan's recent record against Barca is also unfavourable. The Spanish giants are unbeaten in their last seven meetings with the Italians, and have knocked them out of their last two group stage meetings.
Barcelona are aiming to make the quarterfinals for the sixth time in succession, whereas Milan have only won one of their last 10 Champions League knockout games (that was last year's rousing 4-0 victory over Arsenal, which was nearly counteracted with a valiant 3-0 comeback in the return leg).
Massimiliano Allegri's side's form isn't any better against Spanish sides in general. They have lost their last six home games against La Liga opposition, and only earned one point from two encounters with Malaga in this season's group stage.
Mario Balotelli—the catalyst of Milan's recent resurgence, who has scored four times in three games—is cup tied and unavailable for selection. According to Oddschecker.com, the Italians have odds of around 5-1 on a victory—surprisingly long odds for a home team of Milan's calibre in this competition.
There are often statistical cases that can be built to support an underdog in encounters like this. Unfortunately, the numbers suggest the Rossoneri faithful will be leaving the San Siro disappointed on Wednesday evening.