Twelvetrees, 24, replaces injured powerhouse Manu Tuilagi in one of two changes from December’s historic defeat of New Zealand for the RBS Six Nations opener at Twickenham.
The Gloucester player is set to start at inside centre, with Saracens’ Brad Barritt switching to outside, but Lancaster hinted Tuilagi is likely to return to the starting XV for next week’s trip to Ireland.
“This is a great opportunity for Billy. I coached him in the Churchill Cup – it was a winning side, he played No12 and I could see then he had lots of potential and physicality,” he said.
“I have every confidence in him going into the game. Sometimes opportunities present themselves in different ways. We know Manu is going to be fit for next week and we hope Billy puts a marker down and gives us another headache.”
Prop Alex Corbisiero’s injury sees Harlequins’ Joe Marler return at loosehead, while the Youngs brothers are preferred to Danny Care at scrum-half and Dylan Hartley at hooker.
“Scrum-half is the position I spend most time thinking about. Ben Youngs gets the start this time and Danny will come off the bench but both will get their turn during the Six Nations,” Lancaster added.
“It was a tight call there and at hooker. Tom [Youngs] played very well in the autumn. Dylan comes back into the equation but I need to reward the player in the shirt.”
Lancaster also hit back at former Scotland boss Jim Telfer’s claim this week that England players, such as Tuilagi and swallow-diving wing Chris Ashton, were “arrogant”.
“I don’t call celebrating a try showboating,” he said. “It is not what we believe in.”