Brazilian-born Diego Costa could finally make his Spain debut when the world and European champions host Italy in one of more than 60 friendly internationals being played worldwide.
All 32 World Cup finalists will be in action on Wednesday, with France meeting the Netherlands in another heavyweight clash, and there will also be a milestone in little-known Mitrovica when Kosovo make their international debut in a match against Haiti.
These matches are the last chance for coaches to fine-tune their teams and try out new players before they send a preliminary list of 30 players to FIFA on May 13.
The definitive 23-man squads must be confirmed no later than June 2.
Atletico Madrid forward Costa turned down an invitation to play for Brazil last year, prompting coach Luiz Felipe Scolari to angrily claim that he had "turned his back on the dreams of millions."
Spain coach Vicente del Bosque included Costa in his squad for two November friendlies but he was ruled out by injury.
The Italy match, a repeat of the Euro 2012 final which Spain won 4-0, could therefore mark his debut for his adopted country.
"I think he is a great choice and he can bring a lot to the team," Spain and Real Madrid centre back Sergio Ramos told reporters on Monday as he arrived at the team's training camp.
Spain and Italy also met last year in a Confederations Cup semi-final which ended with both sides staggering around the field exhausted after the game went into extra-time in the tropical heat of Fortaleza. Spain won on penalties.
Although the World Cup will be held in South America, the continent will not stage any of Wednesday's matches.
|Costa's decision to play for Vicente del Bosque with Spain has not been popular with the Brazil national team [Reuters]
Hosts Brazil head for South Africa, surprising observers who would have expected them to face top-level opposition, while Argentina - with Carlos Tevez again overlooked by coach Alejandro Sabello - visit Romania.
Colombia's ability to play without Radamel Falcao, should the prolific striker not recover from a knee injury in time for the World Cup, will be tested against Tunisia in Barcelona.
Coach Jose Pekerman has called up Hertha Berlin striker Adrian Ramos, the Bundesliga's second top scorer, for the first time since the 2011 Copa America.
Of the other South American teams, Uruguay visit non-qualifiers Austria, Chile travel to Germany and Ecuador play Australia in London.
Germany coach Joachim Loew has been fretting about injuries and lack of form ahead of his team's match.
"It looks on paper that we have a top team with individuals. But the truth at the moment does not look so good," Loew told reporters.
"We have a lot of injuries, some players have been injured for months, others lack match fitness and some players who are battling to find their form."
African champions Nigeria have recalled former captain Joseph Yobo for their game in Atlanta against Mexico, who staggered to the finals via a playoff against New Zealand.
Cameroon have given Barcelona reserves Macky Frank Bagnack and Jean Marie Dongou an unexpected call up for their friendly against Portugal in Leiria.
Ghana, possibly Africa's biggest hope for success in Brazil, are away to Montenegro while ageing Ivory Coast visit Belgium and Algeria play Slovenia.
Elsewhere, England host Denmark at Wembley, while fellow finalists Switzerland and Croatia meet in St Gallen, Russia entertain Armenia and the United States and Ukraine meet in neutral Cyprus.
Kosovo's meeting with Haiti follows a long struggle for the right to play matches and finally came about after FIFA brokered negotiations with the Serbian FA last year.
Although Kosovo are not members of FIFA, they can now stage friendlies against FIFA members as long as no national symbols, including flags, are displayed or anthems played.
Kosovo invited Manchester United winger Adnan Januzaj to take part in the match, but it was declined.
Kosovo declared independence from Serbia in February 2008 and has been recognised by at least 100 countries including the United States and 23 of the EU's 28 members, but not Russia.