|Hull KR (6) 22|
|Tries: Tilse 2, Lunt, Blair, Wardill Goals: Cockayne|
|Oldham Roughyeds (24) 36|
|Tries: Hope, Lepori 2, Roper, Clay, Middlehurst Goals: Palfrey 6|
Championship side Oldham Roughyeds stunned last season's Challenge Cup finalists Hull KR to reach the last 16.
The Roughyeds, fourth from bottom of the second tier, led 24-6 at the break with tries from Will Hope, Richard Lepori, Steve Roper and Adam Clay.
Shaun Lunt, Dane Tilse, Maurice Blair and Joe Wardill crossed after the break to give the Super League side hope.
But missed conversions proved costly as Gary Middlehurst and Lepori's second try secured victory for Oldham.
Hull KR coach James Webster described his side's performance as an "utter embarrassment".
Rovers, who lost 50-0 to Leeds in last year's final at Wembley, have only won twice in Super League this season and lost 40-0 to Catalans Dragons in their last match.
They were still expected to beat part-timers Oldham, who are in their first season in the Championship after winning promotion from League 1.
Yet Oldham outscored them six tries to five, while Lewis Palfrey's six goals to Ben Cockayne's one gave the second-tier side an ultimately comfortable margin of victory against the hosts, who finished with 12 men after Cockayne was sent to the sin-bin moments before Lepori's try with the game's last move.
Meanwhile, last season's Championship winners and Challenge Cup giant killers Leigh, who knocked out Super League sides Wakefield and Salford, are out after losing 10-8 at League 1 side Toulouse.
Batley Bulldogs are also through to the sixth round after a 28-10 victory over fellow Championship side Featherstone Rovers.
Oldham Roughyeds coach Scott Naylor: "This is probably the biggest win since the club reformed [in 1997]. We spoke about getting to 20 minutes, then 30 minutes and see what happens.
"We didn't expect the half-time score to be 24-6 and we knew they would come out in the second half and have a go after getting a bit of a roasting. For the club, this is something we'll cherish.
"It's a massive day for Oldham and it could be a massive night for the players. I'll go home and have a few beers with my family."
Hull KR coach James Webster: "It was the biggest embarrassment of my career since before I left school. What we dished up was utter embarrassment.
"I've protected these boys since I've been here, but I have to apologise to everyone associated with this club. That is not of a level that's needed to pick up the wage they pick up.
"Supporters give up cars, holidays to follow this club because I deal with these people every day. I understand what people think and it's all true.
"Well done to Oldham because I thought they played very well."
Hull KR: Cockayne, Wardill, Sio, Thornley, Dixon, Blair, Marsh, Tilse, Lunt, Green, Greenwood, Clarkson, Walker.
Replacements: Mulhern, Donaldson, Boudebza, Lawler.
Oldham: Lepori, Clay, Gee, Grimshaw, Chisholm, Palfrey, Roper, Joy, Owen, Spencer, Middlehurst, Langtree, Hope.
Replacements: Ward, Hughes, Files, Thompson
Ref: S Ansell