England and Wales meet for the first time since 2011 on Thursday.
With Wales on top of Group B with three points and England looking to banish Russia's injury-time equaliser from their memories, there is plenty on the line in this battle of the Brits.
We look at five key issues.
1. How much impact will Gareth Bale have?
The Real Madrid star has loomed large over the fixture since it was drawn. England may have the more decorated team, but Bale is the most singular talent on show and has not been shy about taking centre stage. His comments have been wilfully provocative in the build-up, while England have repeatedly said they are not focusing solely on his threat. But make no mistake, Wales' fortunes rise and fall with Bale and how he performs on the occasion could be the decisive factor. Given his roaming brief, England will not man mark him, meaning everyone must be alert.
2. Will Anglo-Welsh relations remain strong?
With England facing the prospect of punitive action from UEFA if their fans are involved in any further disorder following clashes with Russian fans in Marseille, a British derby keeps the stakes high. But the biggest source of antagonism again appears to be Russian fans staying in nearby Lille. On Tuesday evening videos emerged on social media of England and Welsh fans happily mingling, with others joining to show unity against Russian aggressors. Fingers will be crossed the bonhomie persists.
3. Nobody puts Harry in the corner (except England)
Roy Hodgson's persistence with Harry Kane taking corners has become a major debating point in recent weeks. He insists that Kane's delivery marks him out as the man for the job, but dead-ball duty takes the Premier League's top scorer out of the danger area too frequently. Kane's corners against Russia were hardly exceptional either and Hodgson must have given some thought to the likes of Adam Lallana or Wayne Rooney taking their turn.
4. Will the referee allow a British Style game to unfold?
With 45 of the 46 available players plying their trade in the British leagues - Bale being the notable exception - and local bragging rights on the line, a fast-paced, hard-tackling match might be expected. But there is one crucial variable at play: German referee Felix Brych. If he officiates in the traditional continental style there could feasibly be a rush of free-kicks, yellow cards and an increased risk of a red.
5. Do Wales change a winning side?
Having marked their return to tournament football with an emotional victory over Slovakia, will Wales be tempted to switch things up? Joe Ledley is a guaranteed starter ahead of David Edwards if fit but his mere arrival from the bench was remarkable given his leg break five weeks ago and he admits 90 minutes is a long shot. Hal Robson-Kanu also made a strong case for the starting side, bagging the winning goal last time out, and will put Jonathan Williams under pressure for his shirt. Robson-Kanu's presence in attack would also allow Bale greater freedom to rove.