With its destructive back-row combination from the World Cup finally reunited, Wales heads to Twickenham in the unusual position of favourite and with ambitions far higher than just beating England in its own back yard.
Buoyed by their run to the World Cup semi-finals late last year, the Welsh have begun the Six Nations with back-to-back wins to join France as the competition favourites and also leave them on the brink of the Triple Crown.
Getting the better of England - for so long its biggest rival and the defending champion - doesn't appear to be Wales' top target in the Six Nations any more.
"When we won in 1999 at Wembley, it didn't matter that we had come fourth in the championship because we had beaten England but I don't think we look at it that way any more," Wales prop Adam Jones said.
"It's a big tournament and England is the next step. England will be the be-all and end-all on Saturday, but I am not sure it's the same as it used to be."
Wales has won just once at Twickenham in the last 24 years but has a great chance to improve that record now its injury problems have relented.
Sam Warburton returns from a thigh injury to captain the team and join a back row also comprising fellow flanker Dan Lydiate and No 8 Toby Faletau, a trio that was in rampaging form for the Welsh at the World Cup but hasn't played together since.
With first-choice lock Alun-Wyn Jones also back in the pack, England will have its hands full to contain Warren Gatland's side and also stay perfect after away victories over Scotland and Italy.
"To beat the favourites and be three from three would put us in a good situation but the same can be said for them. It's a big, crunch game," England fullback Ben Foden said.
"Any team that can beat this Welsh side in this form puts down a massive marker. Wales must be considered one of the top three or four teams in the world."
England, still winning matches despite being in a transitional stage with a young squad and under interim coach Stuart Lancaster, made four changes in personnel to the team that beat Italy 19-15 in Rome.
Scrumhalf Lee Dickson, No 8 Ben Morgan and lock Geoff Parling will all start for the first time, while Manu Tuilagi was recalled at outside centre after injury for his first appearance since the World Cup.
The most eye-catching change was positional, however, with 20-year-old Owen Farrell switching to flyhalf from centre after No 10 Charlie Hodgson hurt his finger in training.
Farrell has been earmarked as the long-term replacement for the recently retired Jonny Wilkinson, England's World Cup-winning flyhalf from 2003, and is given his first chance at test level to play in his preferred position.
"No one is concerned in the slightest," Lancaster said. "As a management, we know he is a quality player and a grounded person. It's a great opportunity for him and I'm sure he'll be excited by it.
"I wouldn't want to compare any young player to Jonny Wilkinson because I think it sets them up. Owen Farrell is Owen Farrell. His core skills, his basic skills, are very good. He is one of the best young players I've ever coached in that regard."
England will start with its most inexperienced line-up in the Five/Six Nations for 23 years, with 182 caps compared to Wales' 488.
England: Ben Foden, Chris Ashton, Manu Tuilagi, Brad Barritt, David Strettle, Owen Farrell, Lee Dickson; Ben Morgan, Chris Robshaw, Tom Croft, Geoff Parling, Mauritz Botha, Dan Cole, Dylan Hartley, Alex Corbisiero. Reserves: Rob Webber, Matt Stevens, Courtney Lawes, Phil Dowson, Ben Youngs, Toby Flood, Mike Brown.
Wales: Leigh Halfpenny, Alex Cuthbert, Jonathan Davies, Jamie Roberts, George North, Rhys Priestland, Michael Phillips; Toby Faletau, Sam Warburton, Dan Lydiate, Ian Evans, Alun-Wyn Jones, Adam Jones, Ken Owens, Gethin Jenkins. Reserves: Richard Hibbard, Paul James, Ryan Jones, Justin Tipuric, Lloyd Williams, James Hook, Scott Williams.