For most of their international careers, Gianluigi Buffon and Iker Casillas have faced one another but both Spain and Italy are embarking on a new era.
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As well as changes on the touchline - with Giampiero Ventura replacing Antonio Conte as head coach for Italy post-Euro 2016 and Julen Lopetegui replacing Vicente Del Bosque for Spain - the tie between the two nations will see Buffon up against David de Gea, a change from his famous battles against Casillas.
"It will be strange not to see Iker [Casillas]," Buffon said. "What's happening with him is a sign for me.
"The life of an athlete is to first be a protagonist and then to become a spectator, so I will soon have to start preparing for the latter."
The last-16 tie between the two at Euro 2016, in which Italy won 2-0 thanks to goals from Giorgio Chiellini and Graziano Pelle, was one of the biggest talking points, as the defending champions crashed out.
Discussing what Italy did to beat Spain, Buffon believes that Italy's mentality shone through.
"There were a lot of nerves and adrenaline in that game," he stated. "I remember two teams with a strong mentality, but I cannot remember everything that happened.
"We had a very intense game and were excellent mentally, which we will also have to have tomorrow [Thursday]."
Buffon expects to see a different Spain on Thursday, however.
"I expect to see a wounded Spain who are eager for revenge," he continued. "We are two new teams.
"They have not forgotten the defeat, for sure, so we must be united and humble."
Pique: Now that I'm keeping quiet, people value me more
After winning La Liga and the Copa Del Rey with Barcelona last season, Gerard Pique carried that form into Euro 2016 but was unable to do anything as Spain were eliminated by Italy in the Round of 16, losing 2-0.
Since the start of the season, the 29-year-old has been playing at an elite level and his absence saw Barcelona lose their first game of the season, a home game against newly-promoted Alaves.
Though he played in last weekend's 4-3 loss away at Celta de Vigo, Pique scored twice and was one of Barcelona's better performers.
"I'm in good form," Pique said. "I have been playing at a high level for two or three years now.
"Now that I've been keeping quiet, it seems as if people value me more and think I'm play better."
When asked about Spain's loss to Italy, in which the Azzurri played a three-man defence, the centre-back believes that the opposition's system did not affect the game.
"I do not think it influenced the game a lot," he replied. "The formations are there, but there are factors that end up being decisive in winning or losing a match."
Inevitably, Pique was coy when asked about comparisons between Vicente Del Bosque and Spain's new head coach, Julen Lopetegui.
"They are different coaches that work differently, so I will not compare them.
"The Del Bosque era was unique and we will never forget him.
"We are beginning a new stage, and a win against Italy will help us as we look to achieve our objectives."
The fixture against Italy on Thursday will also see Pique face Alessandro Florenzi, Roma's versatile midfielder who scored a stunning goal to earn a 1-1 draw for the Italians against Barcelona in last year's Champions League.
"It was a great goal- he meant it too- but that won't happen again."
Bonucci turned down Manchester United and Chelsea due to son's health
A potential move to the English Premier League was a non-starter for Juventus and Italy star defender Leonardo Bonucci this year due to his son's poor health.
Two-year-old Matteo Bonucci has suffered health problems and has had to undergo surgery in recent months meaning that dad Leonardo did not contemplate a move away from Italy.
Manchester United boss Jose Mourinho was willing to offer 50 million euros for the 29-year-old, who was also interesting Chelsea manager Antonio Conte, having made the central defender a mainstay of his Juve side during his three years in Turin.
Reports in Italy suggest that United will return in January to tempt the former Bari defender to England, although it would appear unlikely that Massimiliano Allegri's side would consider selling a star player in the middle of their campaign.
Bonucci starred in Italy's Euro 2016 campaign - including clean sheets against Belgium and Spain, and scoring the equaliser from the spot against Germany - and is in the Azzurri squad for the upcoming World Cup qualifiers against Spain and Macedonia.
Maldini considers Milan return
Chinese consortium Sino-Europe Sports are expected to complete their takeover of the Rossoneri imminently and the club's future CEO Marco Fassone has reportedly offered Paolo Maldini the position of technical director.
The Chinese consortium are looking for a club legend to act as a symbol of their new regime, with Maldini - who made over 900 appearances for the club - the obvious choice.
"I need clarity and independence," the former Italian defender told Gazzetta dello Sport.
"I love this club deeply but before returning I must be able to meet the new owners and discuss the project to overcome two main obstacles - lack of direct responsibility in the technical area and lack of clarity in my role.
"I've talked for ten minutes with Han Li, the vice president of the investment fund, though it was a brief talk and it did not cover enough about the importance of the role and the project.
"Understanding this more is the minimum I need to accept this or any proposal."
The report also suggest that Maldini - who is willing to return to the club but not at any cost - has met with Fassonne on four occasions over the past month.
Maldini won seven Scudetti and five Champions Leagues during his spell with Milan.