Welsh club Llanelli beat Toulouse 41-34 on Saturday to dump the triple European champions out of this year's competition after the home side had led by 21 points.
In another blow to Toulouse, France captain Fabien Pelous had to leave the field in the 39th minute after badly hurting his left knee.
It was only the third time Toulouse had lost before the quarter-final stage since the event began back in 1995.
Guy Noves's men led by 21 points after fullback Clement Poitrenaud scored his fourth try of the game in the 47th minute, but then fell apart in the final half hour.
Toulouse had the upper hand when Pelous was playing but following his exit, after falling having claimed the ball in a line-out, the match turned in Llanelli's favor.
"Fabien had tests which revealed a major blow to his left knee and his period of unavailability will be determined later," Toulouse club doctor Albert Sadacca said.
Pelous has had an injury-plagued season.
He suffered a rib injury in France's first autumn Test, the 47-3 defeat to New Zealand and then missed the next two matches -- a 23-11 second defeat to the Kiwis and a 27-26 win over Argentina.
Those missed games meant he failed to reach the record in appearances for France, of 111 held by Philippe Sella, leaving him on 110. He only returned on Sunday in Toulouse's 20-19 defeat at Llanelli.
In the Pool 5 table, Toulouse lie third with eight points from four matches with Llanelli in top spot on 18 and Ulster, who beat London Irish 29-13 on Friday night, on 10 points.
If Toulouse win their final two matches with bonus points and Llanelli lose both of theirs, the two teams will be level, but Llanelli would come out on top because they beat Toulouse on two occasions.
"I'm very happy and we showed great temperament and character to react the way that we did ... When we were behind 31-10, I was a little worried, but the try we scored at the end of the first half showed that we could get back at them. With four wins out of four we are in a great position to qualify," Llanelli coach Phil Davies said afterwards.
The six pool winners and two best placed runners-up qualify for the quarter-finals.
In other matches, Wasps scored 11 tries against Italy's Treviso in a 71-5 thrashing, including a hat-trick of touchdowns for wing Paul Sackey, to secure maximum points from the tie and move two points ahead of Perpignan at the top of Pool 1.
And Leicester pulled closer to Pool 4 leaders Munster of Ireland with an easy 57-3 home win against struggling French club Bourgoin.
In other games, it was: Munster 32, Cardiff Blues 18; Leinster 25, Agen 13; Northampton of 36, Overmach Parma 0.
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