Vienna - Unpredictable Latvian Ernests Gulbis out-aced John Isner 23 to 16 in a 6-4, 4-6, 6-4 knockout of the American third seed to reach the Austria Open quarter-finals on Wednesday.
The second-round defeat meant that Isner's already slim chances of qualifying for the eight-man field at next month's World Tour Finals took a major hit.
Isner, the top US player at 13th in the world, stood provisional 12th in the points race to the season wrap-up in London which takes place from November 15-22.
He was among a group of a dozen who at the start of the week were chasing the two remaining qualifying spots.
Vienna top seed David Ferrer, who had to fight through for a post-midnight win at the Stadthalle in his opening match, currently stands on the provisional eighth position behind Japan's Kei Nishikori with those two next in the queue for the year-ender.
Gulbis, who had lost five straight matches at the ATP level before arriving in the Austrian capital, will next face either Croatian seventh seed Ivo Karlovic or Sergiy Stakhovsky of the Ukraine.
Gulbis, who has ridden a ranking roller-coaster in his patchy career, currently stands at a humble 117th in the world.
The Latvian son of a millionaire businessman now stands 3-2 over Isner, who had won their last two meetings.
Gulbis went up an early break in the final set and held the edge until the end.
In a first round match, Italy's eighth seed Fabio Fognini defeated Frenchman Paul-Henri Mathieu 6-4, 3-6, 6-3 in the pair's first meeting since 2009.
Jo-Wilfried Tsonga, the French fourth seed who was runner-up to Novak Djokovic at the Shanghai Masters last weekend, was starting against two-time Vienna winner Tommy Haas later on Wednesday.
German veteran Haas, 37, is fighting back after a third shoulder surgery last season and is ranked at 466th.