Rossoneri will have a mountain to climb in the second leg of their Champions League semi-final of the first act 2-0 during AC Milan vs Inter Milan at the San Siro, thanks to goals by Edin Dzeko and Henrikh Mikhitaryan.
Milan were rocked by a lightning fast start from Inter and they never recovered, with the first goal coming less than 10 minutes in as nobody marked Edin Dzeko from a corner and he fired in first time.
The second just minutes later when Henrikh Mkhitaryan strolled through the middle unopposed to slot past Mike Maignan, and things really threatened to get out of hand from there with the Rossoneri's defence all at sea.
Despite a positive start to the second 45 and with Sandro Tonali hitting the post, there was to be no goal for Milan to cling on for and they are now left hoping for a minor miracle in next Tuesday's return fixture.
The build-up to the game was dominated by Rafael Leao and whether he would recover from an adductor problem in time to start on the left wing, but he was not risked and thus Alexis Saelemaekers took his spot. Barring that, it was the same side that brought success against Napoli and more recently Lazio.
There will never be the words to describe just how overbearing the atmosphere was at a sold-out San Siro, but it was summed up well by the opening minutes as the two sets of fans implored with the referee that he'd got each half call wrong.
Eight minutes into the game, Inter got the early breakthrough and it came via Edin Dzeko who Simone Inzaghi had chosen to start over Romelu Lukaku. Hakan Calhanoglu's delivery from the right was volleyed in first time by the Bosnian into the top corner with Mike Maignan rooted.
Less than three minutes later they had doubled their advantage, and this time it was poor open play marking that was Milan's undoing. A ball from Federico Dimarco on the left was wisely left by Lautaro Martinez, and Henrikh Mkhitaryan strode into the box to finish past Maignan unopposed.
The Nerazzurri had the wind in their sails and almost made it 3-0 when Hakan Calhanoglu ripped a shop off the post from about 25 yards out, and then a cross from the rebound eventually found Mkhitaryan whose shot was this time stopped by Maignan.
Things went from bad to worse for Pioli's side as Ismael Bennacer was then forced to come off with what looked like a knock that he couldn't shake off, and Junior Messias came on in his place.
Tried as they might, it seemed as if every time Milan went forward and attempted to assert a period of pressure, they would just get hit in transition at the other end, with the ball worked from flank to centre quite effortlessly at times by Inter.
The Rossoneri's first real opportunity of the half took half an hour to come, with a nice move down the right side ending with Calabria flicking a first-time shot into the side netting from a Messias cross.
It looked as though things had turned nightmarish moments later when Lautaro took a tumble inside the box under pressure from Kjaer and Tomori and the referee Jesus Gil pointed to the spot, however it was rightly overturned after a VAR check with the contact minimal.
A couple more half-chances followed for Inter and both of them came after deflected shots from Dimaro who was lining up a couple of pile-drivers from the left corner of the box. One fell to Lautaro and the other to Dumfries; both flew over.
Milan fans let Jesus Gil know what they had thought of his first half officiating when the whistle blew after four added minutes, but that was not before he flashed yellows to Krunic and Calhanoglu, for dissent by the former and an arm in the face by the latter.
The 'home' side certainly started the second half of AC Milan vs Inter Milan, much brighter and twice had the chance to work Andre Onana but failed to. The first was when Brahim burst between the lines and curled a shot wide of the far post, and then Messias had an even bigger chance after a diagonal run from the right but also wasted it.
Inter then had their own opportunity to perhaps even put the tie to bed when nobody stopped Alessandro Bastoni's striding run out from the back and he found Dzeko who Kjaer played onside, yet Maignan rushed out and made an important block.
Just short of the hour mark, Pioli elected to make a double change as Divock Origi came on for Saelemaekers while Malick Thiaw replaced a rather tired-looking Kjaer.
In a game and a tie of fine margins, it seemed as though all of them were going against Milan. A nice ball from Origi released Brahim whose cut-back to Giroud saw the Frenchman feed Tonali, yet his shot agonisingly skimmed the post.
Acerbi tested Maignan with a shot from distance that was in the end comfortably saved, with Romelu Lukaku and Stefan De Vrij then coming off the bench before Darmian saw an effort from inside the box deflected wide.
Pioli's final roll of the decide came with less than 10 minutes on the clock as Pierre Kalulu and Tommaso Pobega came on for Calabria and Brahim Diaz.
When Pobega's shot from the edge of the box was comfortably saved in the second minute of four added it was clear that it wasn't Milan's night, and next Tuesday will have to be something pretty special now.