Debutant Twelvetrees scored one of England's four tries in a 38-18 victory over Scotland and produced a classy all-round performance that won rave reviews and pointed to a big future on the Test stage.
The 24-year-old's Twickenham display provoked an immediate debate about the composition of the England midfield in Dublin next weekend, with Manu Tuilagi expected to be fit again.
Head coach Stuart Lancaster now has a selection headache as Tuilagi and Brad Barritt, who is a defensive rock, were key to England's victory over New Zealand in December.
Twelvetrees would bring a different attacking dimension and made a strong case for selection with a confident debut.
"I always wanted to score a try for England at Twickenham. It was a very nice moment," Twelvetrees said. "I have always had belief in myself and what I can do. Stuart and the coaches have really backed me up on that.
"Being in the squad is one thing but being in the team and proving to everyone else around you that you are good enough to help lead them and put together a good attacking team and defensive line.
"I always believed I was good enough, it was just getting a chance to do it. I really enjoyed being out there. I just wanted to get my hands on the ball and do what I do every week for Gloucester.
"I wanted as much ball as I could to do what I do best and I felt like I did that well. As soon as the points started rolling over I felt quite comfortable."
Twelvetrees is a strong defender but it is with the ball that he comes into his own. He carries powerfully and at pace but also offers a second playmaking option in midfield.
His try was from close range but it was scored despite the presence of two Scotland defenders because of the excellent line he chose as he ran onto Ben Youngs' short pass.
Twelvetrees' fledgling partnership with fly-half Owen Farrell is already drawing comparisons with the Jonny Wilkinson-Will Greenwood axis from England's World Cup-winning team.
It is early days but Twelvetrees was happy with how they worked in tandem after just a fortnight training together.
"I made it my goal to get to know guys as quickly as possible and how they play. I watch Owen in the Premiership every week and what he does," Twelvetrees said.
"We sat down this week to work out what would work best for us against Scotland. We communicate well out on the field and you can click."
England's trip to the Aviva Stadium, where their Grand Slam dreams died two years ago, is looming as a potentially pivotal match in this year's tournament.
Lancaster also has other selection decisions to make. If Ben Morgan fails to recover from an ankle injury, Tom Wood could start at number eight with James Haskell on the blindside.
"We are delighted with the way he (Twelvetrees) took the try but his confidence and composure has been good all week. It shows he is ready to make the step," Lancaster said.
"This time last year we had seven players making their debuts and with Billy making his we have a young side.
"There are a few selection debates to be honest. Dylan Hartley and Courtney Lawes did well when they came on. Haskell was outstanding.
"Across the board and with Manu coming back into consideration there will be some selection decisions to make. We need to knuckle down to what will be a massive game against Ireland."
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