Zamalek threw away their lead and conceded a last-gasp goal to suffer their first defeat of the season following a 2-1 loss to promoted Ghazl El-Mahalla in the Egyptian Premier League on Tuesday.
Tunisian midfielder Ferjani Sassi, whose future at Zamalek is uncertain as his contract expires at the end of the season, headed home nine minutes past the hour mark to end Mahalla's resistance.
However, Zamalek were punished for needlessly easing off as Abdo Yehia brought Mahalla level with a deflected shot on 77 minutes.
Sassi was sent-off after receiving a second booking for kicking an opponent in the face while attempting an overhead kick and Mahalla made the most of a defensive mix-up deep in stoppage time to notch a decisive winner through Khaled El-Ekhmimi.
Zamalek failed to extend their lead over defending champions Ahly, who had their league game this week postponed as they gear up for a Club World Cup clash against Qatar's Al Duhail on Thursday.
The White Knights remain on top with 23 points, two ahead of Ahly, who have a game in hand. Mahalla moved up to 10th in the table on 11 points.
Zamalek had territorial dominance in the first half but struggled to carve out real openings, with their rhythm affected by the absence of an out-and-out striker after marksman Mostafa Mohamed joined Turkish side Galatasaray on loan.
Their best chance fell to Ahmed Zizo, who broke clear following a deft long ball from Emam Ashour but his poor control allowed the keeper to close him down on the left hand side of the area.
Zamalek increased their pressure in the second half and the breakthrough finally came when Sassi leapt unmarked to head an inviting cross from Ashour into the bottom corner in the 69th minute.
But Yehia restored parity when a poor headed clearance from Zamalek's central defender Mahmoud Alaa fell to him to wrong-foot keeper Mohamed Abou-Gabal with a deflected shot.
While Zamalek poured forward en masse in search of a winner, Mahalla stunned them from the unlikeliest of sources.
Just before the final whistle, what seemed to be a routine defensive clearance saw central defender Mahmoud Hamdi's pass bounce off teammate Eslam Gaber, who was poorly positioned, to find a Mahalla forward in a one-on-one situation.
Abou-Gabal produced a superb one-handed save to thwart his effort but El-Ekhmimi made no mistake on the rebound to roll the ball into an empty net and give Mahalla a famous win.
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