AC Milan's Serie A title defence is as good as over after Sunday's 5-2 home humbling at the hands of Sassuolo which plunged the champions into deep crisis, while Monza stunned Juventus 2-0 in Turin.
Everything that could go wrong for troubled Milan did at a gloriously sunny San Siro, with two goals ruled out for offside and a shocking defensive display condemning them to another heavy loss after also being hammered by Lazio and Inter Milan in the last 10 days.
Milan will be a whopping 15 points off the Scudetto pace if league leaders Napoli beat fierce rivals Roma in Sunday's late match, and they will also drop out of Serie A's top four if either Roma or Lazio, who host Fiorentina later in the day, avoid defeat.
Next up is the derby against second-placed Inter who thumped Milan 3-0 in the Super Cup less than a fortnight ago as Milan try to end an alarming slump which began with throwing away a two-goal lead to draw with Roma three weeks ago.
"We have to react, we're probably not going to win the title again but we have to fight to qualify for the Champions League," said Pioli to Sky in Italy.
Pioli's team are fourth after allowing Sassuolo to win for the first time since late October thanks to an inspired performance from Domenico Berardi.
The Italian netted his team's fourth and had a hand in three more as Gregoire Defrel, Davide Frattesi, Armand Lauriente and Matheus Henrique all scored in a free-wheeling performance.
Alessio Dionisi's side are 16th but Sunday's shock win took them eight points ahead of Verona who sit just inside the relegation zone and face Udinese on Monday night.
"Milan are having difficulties, it can happen in a period of the season when you play lots of matches but we're still talking about a great team in their stadium," said Berardi.
"To come here and win isn't easy."
- Monza's Juve double -
Monza completed a stunning double over Juve on a day of shocks in Italy, a mature performance belying the fact that the club owned by Silvio Berlusconi are playing in their first ever Serie A season.
Bought by former Italian prime minister Berlusconi in 2018, minnows Monza confirmed their meteoric rise from the lower leagues to move above Juve and into 11th place.
First-half strikes from Patrick Ciurria and Juve old boy Dany Mota were enough for a historic win at the Allianz Stadium for Monza, who also had Gianluca Caprari's brilliant early finish chalked off for offside.
"It's a special day. I'm glad I could do my job and for the boys who worked so hard today," said Mota, who didn't play a senior game for Juve, to DAZN.
Mota's third goal of a season was emblematic of how comfortable they feel at this level, the Portuguese skipping past Wojciech Szczesny and sliding home after great work from Carlos Augusto.
September's 1-0 win over Juve was Monza's first ever in Serie A as well as being Raffaele Palladino's first match in charge.
Sunday's victory came after the latest performance which showed why his team will almost certainly be in Italy's top flight come next season.
Goalkeeper Michele Di Gregorio stepped in with superb saves from strikes by Angel Di Maria, Arkadiusz Milik and Manuel Locatelli when Monza's defence had to hold off a Juventus siege in the second half.
"We all have to be responsible for that first half performance," said Juve coach Massimiliano Allegri.
"In our last three (league) matches we have collected one point and conceded 10 goals in a way that wasn't good enough."
Not even the return of Dusan Vlahovic after three months away could stop Juve from falling to their fourth league defeat of the season.
That, and the points penalty for illicit transfer activity inflicted earlier this month, have left Juve languishing in 13th place and 14 points away from the European places.