AC Milan have never failed to qualify from a European quarter final after drawing the first leg at home 0-0, but all runs come to an end and Barcelona can reach the last four again in the Champions League with victory at 2/7.
A victory for Barcelona would see them reach the Champions League semi finals for the fifth year in succession, which would match the competition record currently held by Spanish rivals Real Madrid.
Barcelona may feel they should be carrying a first-leg advantage to the Nou Camp having dominated possession in Italy and being refused a penalty when Alexis Sanchez appeared to be fouled.
More possession is likely at home and Barcelona can call upon Cesc Fabregas and Carles Puyol after both were rested for the weekend domestic victory over Athletic Bilbao.
Furthermore, Barcelona are unbeaten at home in the competition since 2009 and stuck seven past Bayer Leverkusen in the last round.
However, remaining unbeaten may not be enough this time, as a score draw would send Milan through on away goals.
Milan have already drawn 2-2 at the Nou Camp in the group stages of the competition this season and look set to able to welcome back Alexandre Pato, who has missed the last month with injury.
It is 4/1 that Milan claim a draw, although punters fancying Barcelona to get knocked out may be better taking the 11/4 that the reigning Italian champions qualify.
Alternatively, it is 11/1 in the Champions League odds that Milan claim an unexpected victory, which would be their first on the road in the competition this season.
But their chances of victory, or indeed qualification, have not been aided by troubles travelling to Spain, with flight delays minimising their training time.
Also, there was accusations in the first leg that Milan deliberately failed to provide a slick playing surface at the San Siro to prevent Barcelona playing their typical passing game and the pitch will almost certainly be more to the liking of the hosts at the San Siro.
The game marks Zlatan Ibrahimovic’s first return to the ground since leaving Barcelona in 2010 and he is 5/2 to score in the 90 minutes to provide Milan with what could be a priceless away goal.
For Barcelona, it is hard not to side with Andres Iniesta at the prices to score first at 10/1, particularly if he starts on the left side of a front three ahead of promising youngster Cristian Tello.