AC Milan suffered their first defeat in 10 Serie A games as Sassuolo picked up a richly deserved 2-0 win at Stadio Mapei on Sunday.
The Rossoneri could have closed to within six points of the third and final Champions League spot with victory, but they fell to a third defeat in as many trips to Sassuolo since the latter's promotion to Serie A in 2013.
Sinisa Mihajlovic made good on a promise to start Mario Balotelli, despite criticising the Italy striker's desire, although the Liverpool loanee looked out of sorts on the right wing and lasted just 55 minutes.
Sassuolo goalkeeper Andrea Consigli was nevertheless kept busy in the first half, as Milan spurned a host of clear-cut chances before Alfred Duncan's screamer put the home side ahead against the run of play.
Having wasted a string of opportunities in the first half, Milan created next to nothing after the interval and Nicola Sansone slammed home a well-worked second to move Eusebio Di Francesco's men just three points behind Milan in their own hunt of continental qualification - Gregoire Defrel's late dismissal doing little to derail an impressive performance.
Milan may well look back and wonder how they lost a game in which they ought to have been out of sight inside the first 10 minutes.
Consigli was on hand to deny Giacomo Bonaventura from 25 yards and Keisuke Honda one-on-one before Carlos Bacca ignored Balotelli to his right, only to see his shot deflected wide.
Consigli again reacted smartly to keep out Luca Antonelli's looping header and a fizzing effort from Juraj Kucka, but former Inter midfielder Duncan intervened in stunning fashion midway through the half to put Sassuolo ahead.
Domenico Berardi caught the Milan defence cold, swinging a right-wing corner to the edge of the box, where Duncan was racing in to rifle a left-footed blockbuster into the top-right corner.
Gianluigi Donnarumma prevented Berardi from scoring a ninth goal in six games against the Rossoneri after a weaving run from the left wing by Sansone.
Balotelli's malaise was summed up just before the break as he could only see a left-wing delivery flash across the box ahead of him and Mihajlovic hooked his striker after 10 more listless second-half minutes, in which time Donnarumma had again thwarted the lively Berardi.
Jeremy Menez replaced Balotelli but Sassuolo were well on top by that point and Sansone made sure of the points in the 71st minute after Berardi and Sime Vrsaljko combined smartly on the right amid ponderous Milan defending, which enraged Mihajlovic to such an extent he was dismissed.
Defrel was also given his marching orders after hauling down Kucka in midfield, collecting a second caution.
The numerical advantage was hardly noticeable in the closing stages as the Coppa Italia finalists shambled to a defeat which dents their hopes of a Champions League return in a week where the continent's biggest clubs have reportedly looked to engineer a closed shop at Europe's top table - perhaps Milan's best hopes for now.