Juventus fell to their first Serie A defeat of the season as they were beaten 2-0 by Genoa at the Stadio Luigi Ferraris with on-loan Stefano Sturaro scoring the only goal against his parent club before Goran Pandev sealed the victory late on.
Following his midweek heroics against Atletico Madrid, Cristiano Ronaldo was left out of the squad entirely by boss Massimiliano Allegri for the first time this season when the Portuguese international has been available.
And the Serie A leaders, who came into this match 18 points clear of second-place Napoli, were flat in the early stages, and thought they had conceded a penalty on the half hour mark when the ball struck Joao Cancelo's arm inside the box.
However, after consulting the video assistant referee (VAR), referee Marco Di Bello reversed his decision. And VAR was called into action again on 56 minutes as Paulo Dybala saw his goal eventually ruled out for offside.
Genoa boss Cesare Prandelli, who sensed the momentum was with his side, made positive changes as he sent on Pandev on the hour mark, before bringing on Sturaro on 70 minutes -- and the Italian opened the scoring just two minutes in.
Collecting a pass from Pandev on the edge of the box, Sturaro curled in an effort which bounced awkwardly in front of former Genoa goalkeeper Mattia Perin, who could perhaps have done better to prevent the ball from going into the back of the net.
And, on 81 minutes, Pandev finished off an impressive counterattack with a brilliant finish past Perin.
"I expected a different Juventus," Allegri told Italian broadcasters. "We did not put in a good performance, we made some mistakes and then this goal came out of nowhere.
"Much like the Coppa Italia defeat to Atalanta, we picked the right game to lose, because it's just before the break for international duty, so we have time to unplug and rest.
"I am actually happy for Stefano, because if anyone had to score against us, I'm glad it was Sturaro. He's a lovely guy and suffered so much, out of action for practically a year with that tendon injury, so he deserves it."
The result is unlikely to have any impact on the destination of the Scudetto, while Genoa move up to 12th with victory.
Information from Reuters was used in this report