Burton, 65, originally played the lead role of pathologist Sam Ryan in Silent Witness, the longest-running crime drama currently on TV, from 1996 to 2004.
Now, 17 years on from leaving the Lyell team, she'll join forces with her successor Emilia Fox who plays Dr Nikki Alexander to mark 25 series of the BBC One show.
The storyline sees Sam turn to Nikki and the Lyell team for help after a catastrophic event - she has been trying to usher in democratic health care, but the shooting of the Health Secretary and her husband leaves her reeling.
With any number of options available to investigate what happened, what makes Sam turn to her old team?
Burton said of the show's fans: "I hope they're going to really enjoy seeing this because I don't know of any other character or any other show where this has happened before."
She added: "It was genuinely a really, lovely thing to step into Sam's shoes again and to catch up with who she is now and where she is in her life."
Meanwhile, Fox admitted that it was "nerve-racking" to act alongside Burton, who she described as "the Empress of the post-mortem".
She said: "It's wonderful that we're celebrating with Amanda. We wouldn't be where we are today without her. It's her legacy we live with.
"Sam is such a pioneering figure. Back then, female leads were few and far between. Going into Silent Witness, I felt that there was no way I could take over from Amanda, but the producers said, 'don't worry, we'll take it in a different direction'."
The new series features six episodes due to begin later this month and also welcomes back David Caves and Genesis Lynea to the cast as Jack Hodgson and Simone Tyler.
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