Egypt have won an unprecedented three continental titles in a row starting in 2006 but might not reach the 2012 tournament unless they get back on track in Cairo on Sunday.
They start the game against the 2010 World Cup hosts without a win in their first three Group G encounters.
Bottom-placed Egypt have one point, six behind group leaders South Africa, and anything other than a victory will leave them effectively out of the running marking the end of an era.
The match at Cairo's Military Academy Stadium, moved to a smaller capacity venue in the wake of increasing crowd violence at league games across Egypt in recent months. is one of 21 qualifiers across the continent this weekend.
Cameroon also need a win to avoid being left on an almost equally slippery slope while at the other end of the spectrum Ivory Coast can reach the finals if permutations go their way.
In Group E, Cameroon are five points behind Senegal, who they host in Yaounde on Saturday.
Samuel Eto'o's mantle as Africa's leading striker will be challenged by the impressive Senegal trio of Ligue 1 top scorer Moussa Sow of Lille, Mamadou Niang from Turkish champions Fenerbahce and Papiss Demba Cisse, who got 22 goals in the Bundesliga for Freiburg this season.
Senegal have scored 12 goals in their first three Group E games in the 2012 qualifiers.
If Ivory Coast win in Benin on Sunday and Rwanda do not get full points away to Burundi, Didier Drogba's team will be assured of top place in Group H with two rounds to play.
The Ivorians would become the second side after surprise package Botswana to emerge successfully from the qualifiers and make the 16-team finals in Equatorial Guinea and Gabon next January.
The weekend's extensive programme starts on Friday with Michael Essien's return to the Ghana line-up for their home game against Congo in Group I.
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