Wales and Scotland will launch their end-of-year Test campaign when they meet for the inaugural Doddie Weir Cup in Cardiff in November, it was announced Friday.
Outside of World Cup warm-up or tournament matches, traditionally, leading European countries meet just once annually in the Six Nations.
Wales and Scotland will kick-off this season's Six Nations in Cardiff on February 3 but this year will see them resume rivalry nine months later in the Welsh capital on November 3.
Former Scotland lock Doddie Weir revealed last year he was suffering from Motor Neurone Disease and has since established a charitable foundation to help raise awareness of the condition.
November's match will be the first time Wales have played a Tier One or leading rugby union nation from Europe since they established a four-match end-of-year series 17 years ago.
Autumn fixtures in Cardiff have tended to see Wales up against southern hemisphere giants such as world champions New Zealand, Australia and South Africa.
Playing four internationals in November and December usually means that at least one of Wales' fixtures falls outside World Rugby's agreed 'window' for Tests at that time of year, with the result that clubs are not obliged to release players.
Moreover there are fears that by playing an 'extra' international, countries are risking the health of their star performers in what is, at senior club and Test level, an increasingly brutal game, with concerns over player welfare in general and concussion in particular one of the major talking points in rugby union.
While it is not yet clear how much money from the new fixture will go to Weir's foundation -- there will be a series of "initiatives" over the weekend-- Welsh Rugby Union chief executive Martyn Phillips said the income generated from a fourth Test at the 74,500 capacity Principality Stadium was a financial necessity for the game in Wales.
"We need four international matches in our autumn calendar in order to provide vital funds for the future sustainability of the game in Wales," he said.
"Scotland will be an entirely different prospect outside of the Six Nations Championship, and this is a rare chance for a much broader base of supporters to experience a match of this magnitude."
The match will launch an extended November campaign for Scotland, who will also play three fixtures at Murrayfield against Fiji, South Africa and Argentina.
Scotland coach Gregor Townsend, a former Test team-mate of Weir, said: "Facing Wales on the road is an exciting prospect for our players as we begin the final of year of preparations for Rugby World Cup 2019.
"Four Test matches in four weeks is a very similar challenge to the one that we will face in Japan.
"This additional contest in the autumn will allow us to expose more Scotland players to international rugby and will support our preparations to face three huge matches at BT Murrayfield later that month, and beyond."
The WRU said it would announce Wales' remaining end of year opponents "shortly".