Mark Williams became the latest big name to crash out of the Welsh Open when he lost 5-3 to Dominic Dale.
Dale came from 3-1 down to beat his fellow Welshman for the first time and reach the quarter-finals.
"Everyone was expecting him to win so he was under pressure," he said after seeing off the reigning world champion.
Ireland's Ken Doherty, the world number six and twice a champion in Wales, also made a surprise exit, beaten 5-1 by Hong Kong's Marco Fu.
But Paul Hunter, champion in 1998 and 2002, had no such trouble, racing into the quarter-finals with a 5-0 whitewash of Anthony Hamilton.
Earlier, Steve Davis finally got one over on John Higgins to reach the quarter-finals, having lost 19 straight matches to the Scot since 1997.
The six-time world champion rolled back the years to advance to the last eight of a ranking event for the first time since the Irish Masters last March.
Dominic Dale v Alan McManus
Paul Hunter v Ronnie O'Sullivan
Marco Fu v Stephen Hendry
Steve Davis v Robert Milkins
A jubilant Davis said: "I knew he'd beaten me several times but I had no idea it was 19 in a row."
Stephen Hendry remains on course to defend his title after easing into the quarter-finals with a 5-1 win over old foe Jimmy White.
White scored only 38 points in the closing four frames as Hendry fired in breaks of 95, 56, 54 and 81.
The Scot said: "I'm playing great. When I get in the balls I don't feel like missing and my safety is pretty decent at the moment as well."
Ronnie O'Sullivan coasted into the last eight with a routine 5-2 defeat of Joe Perry.
He said: "I don't feel particularly confident but I just tried to keep it tight and give every shot its full merit."
Alan McManus came from 4-1 down to edge 2002 world champion Peter Ebdon 5-4 in a match which included four centuries.
And Rob Milkins caused an upset with a 5-4 win over world number five Stephen Lee.