The Poland striker was handed the chance to score from the penalty spot after being brought down in the box by Mexico's Hector Moreno.
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With Mexico's supporters doing everything that they could to put the striker off, Lewandowski was tasked with keeping his composure in a high-pressure moment, something that he failed to do.
Stepping up to take the penalty, the 34-year-old was denied by Mexico legend Ochoa who dived to his left and kept the effort out.
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At 37 years of age, Ochoa is a veteran of the game but his save sent supporters in Green into raptures as he kept the Mexicans in the game.
talkSPORT commentator Joe Shennan predicted something was wrong as Lewandowski stepped up to take the penalty, saying: "It's the first time I've seen him look nervous in his career," to which co-commentator Tony Cascarino responded: "When it's not meant to be, it's not meant to be!"
For Lewandowski, the miss sees him extend a miserable run in the World Cup.
Despite scoring shedloads for club and country over the years, the Poland striker is yet to find the net in a World Cup fixture.
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The clash with Mexico was his fourth opportunity to score on the grandest stage of all, but thanks to the heroics of Ochoa, that search will continue for a little while yet.