With the World Cup just a year away, qualifying is becoming more critical, especially in a match between the third-place finisher from 2002 and the reigning European champion.
Besides a match between pair of teams separated by two points, the game pitting Greece against Turkey also features two nations that have shared a mutual animus since the Greeks became independent of the Ottoman Empire almost two centuries ago.
As qualifying enters the final five months of a two-year long campaign, hopes of some teams are becoming more desperate, while others are nearing the end of their journey.
Two-time champion Argentina could be the first team to join the host within the next few days. Defending champion and five-time winner Brazil and three-time champ Italy also are in good shape.
The Turks and Greeks, however, are chasing surprising Ukraine in European Group 2. One is likely to lose out on a place among the 32 qualifiers. Ukraine leads with 17 points, three more than Greece and five ahead of Turkey with five games remaining for all three.
Led by Andriy Shevchenko of AC Milan, Ukraine is on course to qualify for the first time. With a three-point lead, the former Soviet republic can close on their berth with a victory over winless Kazakhstan at home on Saturday.
The Turkey-Greece encounter in Istanbul is vital to both teams.
The Turks, who beat co-host South Korea to take third place three years ago, have decided not to stage the game at the modern 75,000-seat Ataturk Stadium outside Istanbul. Instead, they've opted for the more intimidating atmosphere of the 21,000-capacity Inonu Stadium, home of 10-time league champion Besiktas.
Besides their nearly 200-year animosity, relations between the two nations have been tense since Turkey invaded Cyprus in 1974 and seized the northern third of the island. A self-declared Turkish Cypriot republic was established in the north in 1983 but only Turkey recognizes the breakaway state.
Because of the history between the two nations, it's unlikely many Greek fans will make the short journey. Greece, which won the Euro 2004 title after never winning a game at a major championship, will likely face the "Welcome to Hell" greetings given to visiting teams by Turkish fans.
"We expect to play in a fanatical atmosphere," Greek striker Zissis Vryzas said. "We hope the Turkish fans will support their team -- but nothing more."
Team members from both countries appeared in a television ad, shown in Greece and Turkey, urging fans to keep the peace.
"Sport unites countries," Greek midfielder Stelios Giannakopoulos says in the ad.
For the Turks, who have won only three of seven qualifiers since their best World Cup finish, victory is essential. Although they travel to Kazakhstan in next week's round of games, another loss would drop it five points behind Greece and probably eight behind Ukraine with four games to go.