Former England talisman and current Harlequins director of rugby Dean Richards admitted his side had no-one but themselves to blame after they were beaten 28-27 by a dramatic second-half fight-back from London Irish.
Quins had raced into a 20-3 lead shortly before the interval with tries from Ugo Monye and Tom Guest.
But London Irish's Delon Armitage scored either side of half-time and Australian full-back Peter Hewat contributed 18 points, including an intercept try, to push the Exiles ahead.
Harlequins' England scrum-half Danny Care set up a frantic last 90 seconds with a late converted try, but London Irish held out for their first win since the opening day of the season.
Against Gloucester last weekend Harlequins gave up a 13-8 half-time advantage to lose 24-20, and they were again unable to retain a lead.
"In the first half I thought we were outstanding. We played some superb rugby but we shouldn't have allowed them to score just before half-time," said Richards.
"They shouldn't have been in with a shout but all of a sudden it brought them back within 12 points. As a consequence it gave them a sniff.
"At the start of the second half our territory play was poor. We allowed them to build up the pressure, they scored their tries and caused us problems.
"It comes down to our ability to take the pressure off ourselves, which we didn't do in the first 20 minutes of the second half.
"Against a team like London Irish that pressure is going to tell and we have nobody else to blame but ourselves."
Quins rallied well in the closing stages and Care snuck over from close range to set up a tense finish - but that was only of marginal consolation for Richards.
"I thought the last eight or nine minutes was fantastic. I thought it showed a lot of character - but then we shouldn't have been in that position," he said.
London Irish boss Toby Booth was delighted by his side's resilience as they mounted a dramatic comeback.
Booth said: "That try from Delon just before half-time was vital. If we go in 20-3 down rather than 20-8 it is a different game.
"The momentum shifts and there was a lot of belief in that changing room at half-time.
"I thought we showed an inner desire and determination.
"If you want to be a consistent performer, if you want to play Heineken Cup year in and year out and you want to challenge for trophies that is the kind of performance you have to put in.
"I see that as a development of the mental side of our game as well as the statistics saying it was a great turnaround."
After Ireland's heroic big-game hunt of the Springboks and Scotland's six-try runaround of the Pumas, the challenge of engineering the most spectacular win of the autumn series now falls on Wales, writes Peter Jackson.