Barcelona return to the scene of one of their toughest defeats in recent years, as San Siro has been tough on them recently. Add to that the tension of facing former teammate Zlatan Ibrahimovic, whose biography roughs up coach Pep Guardiola, and there is plenty of intrigue ahead.
Barca sans success at San Siro
Almost 5,000 Barcelona fans will be in the San Siro Wednesday night to see the European champions play AC Milan in a key Group H Champions League game, the biggest travelling support in the Catalans' history for a group stage game.
Both teams are already through to the last 16, and a victory for Barca will guarantee them pole position. The San Siro holds mixed memories for Barca, as they were beaten when they last visited Milan in the 2010 semi-finals against Inter.
Inter were defensively obstinate and widely criticised for their "anti-football", but they won the game 3-1 and Barca were eliminated.
It was a defeat which, in hindsight, prevented Barca winning three consecutive Champions Leagues and set the template for teams attempting to avoid defeat against Pep Guardiola's side.
Previous visits against Milan, rather than Inter, were happier for Barca. They overcame Milan in the semi-final on the way to Champions League success in 2006 - a single goal all that separated the teams in two absorbing clashes.
The giants did not meet again until this season, when first and last-minute goals saw Milan draw 2-2 with Barca at Camp Nou in September.
Barca head the group after four games, with 10 points to Milan's eight, but they will be without the injured Andres Iniesta and Adriano against the Italian champions, plus the banned Daniel Alves and assistant coach Tito Vilanova, who is hospitalised in Barcelona.
Much focus will be on Zlatan Ibrahimovic, who had a turbulent season with Barca in 2009/10 and has been outspoken about his former coach in his recent autobiography, I am Zlatan. The Swede acknowledges that he left "the best team in the world" last season, but he did not have much choice.
Guardiola wanted him out, just as, a year previous, he had wanted to get rid of Samuel Eto'o, who had been part of the Ibrahimovic transfer.
In an attempt to take the attention away from Ibrahimovic, Sergio Busquets, his former teammate, said after Saturday's 4-0 league victory against Zaragoza that Barca were playing "against Milan, not against Ibra".
Even he knows, though, that all eyes will be on any potential flashpoints between the Swede and Guardiola. And on whether Barca can make another step towards banishing the memory of 2010.