Katy Perry duets with autistic girl in 'Too Many Stars' - video
Perry was promoted as appearing at the autism benefit for a special performance of her hit 'Firework' in honour of a lucky fan.
That fan turned out to be Jodi DiPiazza, a young girl who has coped with her autism diagnosis through music.
DiPiazza accompanied Perry in the advertised performance of 'Firework', which left many in the audience in tears.
Night of Too Many Stars host Jon Stewart even took a few moments to regain his composure before continuing the benefit.
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Perry tweeted about the memorable collaboration after taping Night of Too Many Stars.
"I will never forget last night. It was the most important moment thus far of what I do," Perry wrote.
Perry's appearance on Night of Too Many Stars airs on Sunday, October 21 at 8/7c on Comedy Central.
All proceeds from the event go towards autism education programmes.