The Conservative party leader was addressing the annual party conference in Manchester, during which she apologised to the membership for the general election debacle in June which lost the Tories their overall majority in Parliament.
However, she was forced to pause as comedian Simon Brodkin handed her what he claimed was a "P45" from Boris Johnson, the embattled foreign secretary who is widely known to harbour party leadership ambitions.
Brodkins intervention was described as a "massive" security breach at the event, with local police now investigating how he was allowed to get that close to the Prime Minister.
Greater Manchester Police confirmed that the prankster, now in custody, had managed to acquire official accreditation to the event.
"In light of the arrest during the Prime Ministers speech we are working with the police to review the accreditation process and security arrangement for the Party Conference," a Conservative party spokesperson said.
"Boris told me to do it. He's left me in the lurch," the comic who posed as a media photographer told reporters in the midst of the chaos.
He was quickly escorted from the hall by security to shouts of "out, out, out" from the audience and May was given a standing ovation for deflecting attention by saying she wanted to hand over a similar termination form to Opposition Labour party leader Jeremy Corbyn.
Brodkin, best known for his comedy character Lee Nelson, rose to fame after gate-crashing a FIFA football press conference and throwing dollar bills at the outgoing president Sepp Blatter, accused of corruption.
But his interruption was not the end of Theresa May's woes, as she was then hit by a severe coughing bout which meant she was unable to complete her sentences without having to pause for regular sips of water.
She was even handed a cough drop by Cabinet colleague, UK Chancellor Philip Hammond, which she accepted and joked with the audience about getting something free from the country's finance minister.
But overall her party members welcomed Mays stance in offering an apology for the failed general election campaign, which she said had been flawed because it was "too scripted, too presidential".
On Brexit, May said she was "confident that we will find a deal that works for Britain and Europe".
She also reassured European citizens living in the UK that "you are welcome here" and urged negotiators to reach agreement on this policy "because we want you to stay".
The speech had been billed as her most personal one yet in an attempt to soften her public image, something she tackled head on by dismissing her characterisation as unemotional and an ice maiden and making a compassionate case for her leadership style.
To add to May's troubles, the letters from the conference stage backdrop began to fall off one by one and read a garbled version of "building a country that works for everyone" by the end of her speech.
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