Lyon limped from the field early in the third session of day three on Thursday, immediately appearing in significant discomfort after running in to attempt a catch.
Australia may have to wait some time to determine the full extent of Lyon's injury, given he was yet to be booked in for scans on Thursday evening.
But in a series already full of comparisons to the brilliant 2005 Ashes, the fear for Australia would already be that this is their Glenn McGrath moment.
McGrath's rolled ankle turned the series after he trod on an errant ball before play on day one at Edgbaston, allowing England to fight back after a big first Test loss.
The ramifications of Lyon's right calf injury at Lord's could also be monumental.
This Test was his 100th in a row, highlighting not only how good he has been for Australia with 496 wickets but the fact no other spinner has had to play the primary role since 2013.
The immediate flow-on effects are also significant, with Australia's quicks left without a frontline spinner to hold up an end at Lord's and a three-day turnaround into the next Test at Headingley looming.
Travis Head and Steve Smith shared overs on Thursday evening, but neither will pose the same threat as Lyon in the fourth innings of this match.
"It's not ideal, particularly your spin bowler," Smith said.
"It's a (one-person) role. Batters I suppose there's loads of us around so it's a bit different. Obviously Nathan, if he's no good, he'd be a huge loss.
"However Todd Murphy is waiting in the wings. He has been bowling beautifully in the nets and bowled really well in India when he got his opportunity as well.
"I'd be confident if he came in he'd do a terrific job for us, but fingers crossed Nathan's alright."
Murphy will almost certainly be the man called in for Australia if Lyon is ruled out beyond this Test, as the only other spinner picked in the initial Ashes squad.
The 22-year-old impressed in India earlier this year with 14 wickets at 25.21, after playing only seven first-class games prior to his February Test debut in Nagpur.
Murphy already has the backing of Australia's former spin, and Lyon's chief mentor, John Davison this week, who told AAP last week that Murphy would be ready to one day replace Lyon.
"Todd Murphy is well ahead of the game in terms of his development," Davison said.
"If something happened to Nathan I think Todd could come in.
"Don't expect him to do what Nathan does straight away, but if he had the same opportunities, then I am pretty confident he would be able to get there.
"Murph is pretty mature in terms of his bowling for someone his age."
