The Prince of Wales and Duchess of Cornwall will meet Pope Francis in Rome on the penultimate day of their tour of Italy.
Charles and Camilla will have an audience with the leader of the Roman Catholic Church at the Vatican.
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Pope Francis, 80, the former Archbishop of Buenos Aires in Argentina, was the first non-European pope in more than 1,200 years and the first Latin American pontiff when he was elected as the 266th head of the Catholic Church four year ago.
On Monday night during an acceptance speech for a major award Charles spoke of the enduring bonds between the UK and Italy less than a week after Theresa May triggered the start of the nation's withdrawal from the European Union.
Charles praised the "partnership'' that has benefited the economies and societies of both countries during an address to a gala dinner in Florence that saw him receive the Renaissance Man of the Year award.
The heir to the throne is on a nine-day tour of Europe with the Duchess of Cornwall which has been widely interpreted as a bridge-building exercise with the continent as Brexit begins.
The last time Charles travelled to the Holy See - the jurisdiction of the Catholic Church in Rome - to meet the Pope was in 2009. He had a private meeting with Pope Benedict XVI.
The royal couple are likely to be greeted by a guard of honour formed by the famous Swiss Guards who protect the Pope.
A traditional exchange of gifts will also take place but it is thought the Duchess will not wear black or a mantilla - a lace veil - as Vatican protocol usually dictates.
Before the meeting with the Pope the royal couple will visit the British School in Rome, while Charles will attend a climate change meeting and visit the English College.