The 24-year-old was called upon after Manu Tuilagi, who scored in the 38-21 win over New Zealand last time out, was ruled out with an ankle problem.
Twelvetrees' inclusion is one of just two changes to the side that beat the Kiwis with Joe Marler replacing Alex Corbisiero, who has a knee problem, at loosehead prop.
Lancaster insists Twelvetrees' debut is just reward for his form with Gloucester domestically and he wants to lay a case for more starts against Scotland.
"Billy gets a start and it is a great opportunity for him. With Manu being out he has got a chance to put a marker down now," said Lancaster.
"He has trained really well. He made it into the EPS squad full-time which I think was important for him from a confidence point of view.
"He has played extremely well for Gloucester all of this season really. So it is a great opportunity for him. He has been on a gradual development curve.
"I worked with him during the Churchill Cup a couple of years ago. I have coached him quite a few times and I have always seen that his distribution and kicking game is excellent.
"But I think he has added to that in terms of his contact work, his physicality, his defence and more importantly his communication and confidence."