Falcao's omission from the tournament has led to a rethink in attack for Jose Pekerman's side, which is not short of options to fill his position.
It begins its campaign without a number of key players after midfielder Edwin Valencia and striker Radamel Falcao were ruled out of the competition through injury.
Falcao’s absence is a big blow and means Pekerman is likely to opt for Sevilla striker Carlos Bacca instead, with River Plate’s Teo Gutierrez playing off him in a 4-4-2 formation, but the Argentine coach is yet to decide on a replacement for deep-lying midfielder Valencia.
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Captain Mario Yepes will start at the back, despite his advanced age of 38, although it is unclear which of the other defenders will partner the experienced Atalanta man against Greece.
Further forward, Jackson Martinez appears to have fallen out of favour with Pekerman amid rumours of a bust-up between player and coach, and the Porto man looks set to start on the bench against Greece.
Whichever team turns out on Saturday, Colombia is likely to take the initiative against a Greece team built on a solid back four.
Fernando Santos’ side conceded just four goals in 10 games in qualifying, fewer than any other team in Europe – and all of those were away from home.
Much like in its 2004 European Championship win, Greece’s recent results have come off the back of a disciplined defense and a strong collective effort, boosted by counterattacking football and a successful strike rate from set pieces.
Greece beat Bolivia 2-1 in its last friendly following a four-game goalless streak and is expected to start with a 4-3-3 formation on Saturday, although that will revert to more of a 4-5-1 system when it is defending.
Santos lost Schalke defender Kyriakos Papadopoulos well before the tournament, but has no major injury worries ahead of the game against Colombia. Sokratis Papastathopoulos has recovered from a biceps problem and should start, with winger Panagiotis Tachtsidis also expected to shake off an ankle injury in time for Saturday’s game.