It will be the fifth edition in a row that the two heavyweights have met head to head at a European Championship.
When Italy and Spain meet in Gelsenkirchen on Thursday, they will write a new chapter in what has developed into the most intense head-to-head rivalry in European Championship history.
No two countries have met more often at Euro tournaments than the Azzurri and La Furia Roja -- the Red Fury -- who will line up against one another for the eighth time since 1960.
It will also be the fifth edition in a row that the two heavyweights have met head to head at a European Championship.
That remarkable run began in 2008, when eventual winners Spain beat Italy in a quarter-final, and it actually spans six matches: they met twice in the 2012 tournament including the final that year, which was also won by Spain.
Over much of the country's sporting history, Spain's fans looked enviously across the Mediterranean Sea as Italy racked up four World Cup titles and the Azzurri battled for European supremacy with the mighty Germans.
"The never-ending torrent of some the best centre halves in history always gave them the upper hand, a rock which Spain smashed into time and again," journalist Javier de Paz Fernandez wrote in El Confidencial, a Spanish news website.
But of the three Euro crowns won by the two countries over the last four tournaments, two have gone to Spain, underscoring their rise as a soccer superpower that also saw them crowned world champions in 2010.
In the most recent European Championship showdown, Italy defeated Spain in a nail-biting Euro 2020 semi-final that went to penalties at Wembley.
Federico Chiesa curled a shot past Unai Simon before Alvaro Morata beat Gianluigi Donnarumma from close range to secure a 1-1 draw. Morata and Dani Olmo missed in the shootout, and the Azzurri advanced to the final, beating England also on spot kicks.
In a last-16 encounter in 2016, Italy were again victorious when defender Giorgio Chiellini scored from close range and Graziano Pelle volleyed home in the dying moments for a 2-0 win.
But in their most important meeting in all competitions, Spain triumphed in the final of Euro 2012 when Vicente del Bosque's all-conquering team thrashed Italy 4-0 in Kyiv.
David Silva started the rout with an angled header from a Cesc Fabregas cross and Jordi Alba made it 2-0. Late goals by substitutes Fernando Torres and Juan Mata earned Spain what remains the biggest win in a European Championship final.
That Euro title was the second in a row won by Spain who were crowned world champions in between at the 2010 World Cup in South Africa.
The stakes will not be as high in Thursday's Group B game at the Arena AufSchalke. Spain and Italy both won their opening matches against Croatia and Albania respectively and look well placed to advance into the knockout rounds.
But if they finish first and second in the group, they could be on course for another meeting, this time in the final in Berlin on July 14.
Both sides have shown a different style of football in Germany from what fans typically expect.
Spain thrashed Croatia 3-0 in their opener on Saturday playing a faster, more direct approach than the possession-based "tiki-taka" style which saw them crowned European champions in 2008 and 2012 as well as World Cup winners in 2010.
With their golden generation of pass masters Xavi Hernandez, Andres Iniesta and Xabi Alonso long gone, under new manager Luis de la Fuente, Spain have transitioned to a more flexible approach which is better suited to the young, versatile squad at his disposal.
Against an ageing Croatia side, Spain applied a relentless high press combined with quick transitions that seemed to catch their rivals off-guard.
"We are turning the national team into a team that have many faces," De la Fuente told a press conference on Saturday.
"The other countries no longer know what kind of attack we are going to implement and this is a reason to be very happy because it could put Spain back on the level that is expected from us."
With doubt surrounding the status of midfielder Rodri and captain Alvaro Morata after they picked up injuries against Croatia, De la Fuente, 62, has been keeping his cards close to his chest for Thursday's match, closing Spain's practice to the media for two consecutive days.
Defending champions Italy, beaten 4-0 by Spain in the 2012 final, see little point in trying to disguise their intentions.
Tasked with restoring belief for fans devastated by their failure to quality for the last two World Cups, manager Luciano Spalletti has put his own mark on the side since taking over last year after winning the Serie A title with Napoli.
Steering clear of Italy's traditional 'defence-first' Catenaccio system, Spalletti has implemented a more attack-minded approach, which they used to great effect in beating Albania 2-1 in their opener.
Under Spalletti Italy seek to control possession and dominate small areas of the pitch with intense pressure, allowing Nicolo Barella and Lorenzo Pellegrini to service forwards Davide Frattesi and Federico Chiesa on the wings.
If styles make fights, Thursday's match in Gelsenkirchen should be a cracker.
