Since taking the reins after the 2011 World Cup Lancaster's England have beaten or drawn with all tier one nations aside from Wales - two defeats, including last year's humbling at Cardiff, is their record.
Optimism is high that a fourth straight loss - Wales also beat England in a 2011 World Cup warm-up match - can be avoided however.
It's borne out of the youthful exuberance injected into England's backline, the consistency of selection - Ben Morgan in for the injured Billy Vunipola is Lancaster's only change - and the palpable progress demonstrated on the pitch with victory over Ireland last time out.
His side has also rapidly developed since that defeat in Cardiff - 11 Welshmen survive from that match but only four Englishmen have been selected in the same position they filled at the Millennium Stadium.
At first neither side wanted to lay claim to the favourites tag, now they both do and each side knows that defeat all but renders their RBS 6 Nations title aspirations redundant.
Lancaster knows it's time to deliver silverware. In both previous RBS 6 Nations campaigns, four wins from five was enough for second and while that is the best they can do this year, he believes it may well secure top spot. First however, they must reckon with Wales.
"All the talking is fine but we have to make sure we deliver on the field," said Lancaster.
"It's a big game, a tough game, but we think we're ready.
"Looking at the quality of their team, they are full of British Lions. We don't have so many but, come the day, let's see what happens.
"We respect them and they have got more to their game than people give them credit for. The gain line is important but I'd be surprised if they don't have a few tricks up their sleeve as well.
"We have an opportunity to play against a team that is strong in lots of areas. We have a chance to test ourselves."
Wales' victory 12 months ago was based on their dominant set-piece and six of the eight forwards survive.
Power also played a considerable part and with Jonathan Davies resuming his centre partnership with Jamie Roberts and George North returning to the wing, they have it in abundance.
Warren Gatland - whose first match in charge of Wales was a 26-19 victory at Twickenham in 2008 - has been dealt a late blow by the news Luke Charteris misses out with a neck injury but Jake Ball, although an international novice, is no slouch.
Pride was restored in the Wales camp with a hefty win over France, brought about by a few harsh words from Gatland following a listless defeat in Dublin - their first Championship defeat on the road since 2011.
This will also be the last time Wales travel to Twickenham prior to the 2015 World Cup, a point not lost on Gatland.
"It's a big game psychologically for both teams because we have to go there next year as well. That's going to be even bigger than this Sunday," he said.
"We have two big games at Twickenham in the World Cup against England and Australia.
"But, if we can win on Sunday, that's four in a row against England and if we then win the Six Nations' as well you (opposition) start having a few doubts.
"After a disappointing performance against Ireland I thought we played exceptionally well against France.
"What pleased me was the maturity we showed particularly in closing the game out after being up at half-time.
"Part of my job for this week is to build the players up to have the self-belief that we are good enough to go to Twickenham and win.
"It has definitely been a bridge too far for a number of Welsh players in the past but we're not thinking like that. We won there two years ago.
"They (England) are all saying they have learnt some pretty harsh lessons from last year.
"All the talk is that the boys have turned into men and they have grown up and learned.
"Time will tell, won't it? We'll see on Sunday."