Fernando Verdasco stunned fellow Spaniard and second seed Rafael Nadal in the Miami Open on Sunday, while Stan Wawrinka was also eliminated.
Verdasco - the 29th seed at the ATP 1000 event - defeated Nadal 6-4 2-6 6-3, while Adrian Mannarino - the 28th seed - trumped Wawrinka 7-6 (7-4) 7-6 (7-5).
Nadal looked to have claimed decisive momentum against Verdasco when he reeled off five straight games to level the third-round match at one-set all.
But after Verdasco broke Nadal in the fourth game of the third set to lead 3-1, the world number three had few answers, as his compatriot went on to triumph in two hours, 17 minutes.
Verdasco hit 29 winners to just 18 from Nadal, while the 31-year-old also saved nine of 12 break points he faced.
Andy Murray can chalk up his 500th career singles victory in the fourth round when he meets Kevin Anderson, after the pair had straight-sets victories.
Third seed Murray was too good for Santiago Giraldo, the 27th seed succumbing 6-3 6-4.
Anderson, the 15th seed from South Africa, got past 24th seed Leonardo Mayer 6-4 6-4.
Gael Monfils won an all-French battle over Jo-Wilfried Tsonga 6-4 7-6 (7-4), the 17th seed progressing to a date with eighth seed Tomas Berdych - who saved match points in three different games to beat Bernard Tomic.
Tomic took the first set and was 4-0 up in the second, before eighth seed Berdych came back to win 6-7 (4-7) 7-6 (7-3) 6-1.
The Australian 25th seed held two match points in the eighth game of the second set, and one each in games nine and 10 - but could not convert, and ended up losing 12 of the last 15 games.
Juan Monaco downed 23rd seed Guillermo Garcia-Lopez 7-5 6-4, while Dominic Thiem outmuscled Jack Sock 6-4 6-3.