Care scored the only try for Quins in their narrow win at Franklin's Gardens
Danny Care's try helped Harlequins to a shock victory as leaders Northampton were beaten at home for the first time.
Stephen Myler and Nick Evans exchanged penalties, before the home side went ahead on the stroke of half-time through a penalty try.
Care's charged-down try levelled the scores seven minutes into the second half and Evans added two penalties to give the visitors a six-point lead.
Replacement Shane Geraghty then kicked a penalty but Harlequins hung on.
The Saints had the better of the first half with more possession but struggled to break down a strong Quins defence.
Northampton's pressure was finally rewarded when Myler's penalty gave them the lead after 26 minutes, but this was replied to only three minutes later, when Evans responded with a penalty kick of his own.
Harlequins soon found themselves two men short with John Andress and Nick Easter shown yellow cards, as the visitors came under tremendous pressure in the scrum.
The six-man Quins scrum stood no chance at the next engagement and gave away a penalty try, which Myler converted with the last kick of the half to give the Saints a 10-3 interval lead.
The visitors managed to hold out for the first 10 minutes of the second half still two men short and, with both Andress and Easter back on the field, their tenacity was rewarded, when Care charged down a clearance kick from Myler to score a try which Evans converted to bring Quins level.
Harlequins grew in confidence and Evans kicked two penalties to give his side a six-point lead.
Northampton replacement Shane Geraghty reduced the arrears with a penalty but the Quins held on for an impressive victory.
Northampton Saints director of rugby Jim Mallinder told BBC Radio Northampton: "You never see (defeats) coming. But when you don't play particularly well, and it ends up close, sometimes it goes your way and sometimes it goes their way.
"We put them under pressure and we should have capitalised on that, with two men up.
"It's not good to have weeks off but that's the way it happened and we've lost the game now, and we have to focus on beating Leicester."
Harlequins coach Conor O'Shea: "It was a tremendous result in adversity. It's as adverse as you could get, 10-3 down at Franklin's Gardens with only 13 players.
"You can't coach that, it is all down to the hearts of the players and I am so proud of them.
"I am really pleased that we have broken our away day hoodoo and this gets us back in the mix in the Premiership."
Replacements: Brooker for Cairns (60), Lambert for Andress (64), Vallejos Cinalli for Robson (52), Skinner for Guest (75). Not Used: Collier, Dickson, Clegg, Casson.
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