Spanish giants Real Madrid were surprisingly beaten 1-0 away by Athletic Bilbao on Saturday, on an early goal from Spain striker Fernando Llorente, dpa reported.
The shock defeat means that leaders Barcelona will open up a five- point gap on Real if they manage to beat fifth-placed Sevilla later Saturday at home.
Real have 41 points from 18 games, while Barca have 43 from 17.
"We worked really hard for this win," said Bilbao midfielder Markel Susaeta, "and the fans were just wonderful. They really helped us tonight."
The memorable win takes Bilbao - the only team in Europe's major leagues not to sign foreign players - up to seventh.
The Real players left the field without comment, astonished at losing a match in which they enjoyed 62-per-cent possession and a plethora of clear goal chances.
This is the first time that Real have lost in old San Mames since 2004, and their third league defeat this season.
The Bilbao "Lions" made a fierce start, roared on by the most passionate fans in Spain.
In the second minute, first Carlos Gurpergui and then Gaiza Toquero hit Iker Casillas' posts. Then Llorente made it 1-0 by heading in a dangerous corner.
Real dominated from then on but lacked a cool finish with Gonzalo Higuain injured.
Karim Benzema hit the Bilbao post and Cristiano Ronaldo and Kaka came close to equalizing three times each, only to be foiled by superlative goalkeeper Gorka Iraizoz.
Gurpegui was sent off in injury-time, as Real lay siege to the Bilbao goal.
San Mames then noisily celebrated the unlikely victory of an all- Basque team of youngsters over the world's most expensive team.
Earlier Saturday, Osasuna kicked off the 18th round of matches with a 2-0 home win over lowly Espanyol.
The hosts were two goals up within nine minutes, taking advantage of some sloppy defending from Espanyol.
Winger Juanfran gave Osasuna the lead in the seventh minute with a near-post shot, after a short corner from Javier Camunas.
And just two minutes later, old warhorse Walter Pandiani made it 2-0 by heading in a far-post centre from Camunas.
Osasuna had young midfielder Ruper sent off five minutes before half-time, but Espanyol defender Facundo Roncaglia followed him into the dressing-rooms straight after the interval, making it 10 men per team.
Espanyol never looked capable of turning the match around in chilly Pamplona. They are now seventh from bottom, while Osasuna move up to 12th.