Harlequins' 10-match winning streak came to an end as London Wasps held on for a 17-16 victory at the Twickenham Stoop.
The result is Quins' first defeat in all competitions since November and means that Leicester Tigers are one point ahead at the top of the Aviva Premiership.
Wasps raced into a 14-0 lead with two tries in the first 13 minutes, one each for wingers Tom Varndell and Christian Wade.
Varndell picked off an interception to go in under the posts and Wade finished off a passing move, a score that was confirmed by the TMO. Stand-off Nicky Robinson, who had missed an early penalty shot, converted on both occasions.
Robinson's opposite number, Nick Evans, had also been off-target with his first penalty attempt but corrected that error to his side on the board in the 18th minute.
Wasps lost centre Chris Bell to the sin-bin and Quins took advantage to get back in the contest, Matt Hooper crossing for the score.
Evans added the conversion and brought the first half to a close with his second penalty to reduce Quins' deficit to 14-13 at the break.
Wasps produced a fine defensive effort in the second half and Robinson's 60th-minute penalty padded their advantage to four points.
Evans set up an exciting finish with his third penalty on 72 minutes, taking his personal haul to 11 points, but missed another chance two minutes from time to seal Quins' fate.
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