With the scores finely poised at 1-1 and just a minute of extra time remaining, Ghana were awarded a spot-kick when Uruguay's Luis Suarez used his hand to block a goal-bound header.
The referee brandished a red card for Suarez and pointed to the spot, and up stepped Gyan knowing that a goal would see his side through to a historic World Cup semi-final.
With the world's eyes upon him, the 24-year-old sadly missed the target and the game went to a penalty shoot-out that the South Americans eventually won 4-2.
Gyan was brave enough to put himself forward a second time and converted Ghana's second spot-kick, but was inconsolable at the final whistle after failing to seal the win initially.
"We said to Asamoah that anyone can miss a penalty and it is part of football and it was the only mistake he made," said fellow Black Stars star John Paintsil.
"In fact, it was not a mistake at all. It is part of football and he kicked it from his heart and we all wanted to win the game.
"We have been talking to him. He is feeling bad about that. It is not easy just to forget about something like that.
"As his team-mates, we have to keep him with us and talk to him about it so he can forget about it as soon as possible.
"He is a young lad and, if he continues to think about it, it is going to affect him. We will make sure that he will get through this."