Lock Jim Hamilton will make his first international start and win only his third Scotland cap in Saturday's Calcutta Cup clash at Twickenham.
His previous two international appearances came from the bench, against Romania and Australia last November.
However, the 24-year-old will be on familiar ground, having played in front of almost 60,000 fans at Twickenham for club side Leicester Tigers against Sale Sharks in the Premiership championship final last May.
He will also be confronting a few familiar faces; four of England's starting XV are club-mates at Welford Road, while another two are likely to feature at some point from the bench.
Hamilton will be going head-to-head on Saturday against Louis Deacon - a good friend but also his chief rival for a starting berth at club level - which should add an extra measure of spice to Saturday's contest.
"I expected a few Leicester boys to be involved. I've been asked a few times about whether that bothers me but all I can say is that I play with these boys week in and week out so I don't feel I have anything to fear,' said Hamilton, who qualifies for Scotland through his Glasgow-born father.
"And they are going to have to change their line-out codes, because I know that a lot of their line-out moves are the same as the ones we use at Leicester."
Standing tall at 6ft 8ins and weighing in at just under 19 stone Hamilton is no shrinking violet. And he says he is looking forward to putting his considerable frame to good use against England's huge pack.
"They are going to be really physical and try to dominate us up front I would imagine. I think they've gone for the biggest team possible but that suits us fine because we like to play quick rugby and we'll try to move them around a bit. It should be interesting," he said.
"Obviously I've not been picked to sprint down the wing or to kick drop-goals. I'm there to impose my size and hopefully I can do that.
"It's going to be the biggest game of my life, so I just can't wait."
Peter O'Mahony was named man of the match against England last month
21 April 2017, 7:22pm
Peter O'Mahony's performance in the RBS 6 Nations finale for Ireland against England was crucial to his selection for the British & Irish Lions on Wednesday, Ireland and Lions defence coach Andy Farrell has revealed.