The meeting with Martin McGuinness in a Belfast theatre, 14 years after the Irish Republican Army (IRA) ended its war against Britain's claim to Northern Ireland, will be the final major handshake in a peace process whose success has been studied around the world.
There has been scattered opposition from dissident Irish militants and from some of the IRA's victims. But the vast majority of the province's politicians backs the meeting, the first between the queen and a senior member of the IRA, or its political wing, Sinn Fein.
"This closes the circle," Brian Feeney, a historian of the Irish republican movement, said. "All the important people in Britain and Ireland have met each other and acknowledged each other. It brings Sinn Fein into the mainstream."
McGuinness previously shook the hand of the once fiery, anti-Catholic Unionist leader the Reverend Ian Paisley, who later joined a power-sharing provincial government with the former IRA man.
The meeting with the queen is so sensitive that officials on Tuesday afternoon were unable to say whether it would be open to the press, or even if a planned handshake would be photographed.
The queen regularly meets senior Unionist politicians, who want Northern Ireland to stay inside the United Kingdom, but not Sinn Fein, the largest party representing nationalists who want a united Ireland.
McGuinness, who is deputy first minister of Northern Ireland's power-sharing government, is a hero to republican hardliners, but has long been a hate figure to Unionists, many of whom harbour deep suspicions about his past.
He admits he was on the front line in the war with British forces, including on Bloody Sunday in 1972 when troops shot dead 13 unarmed protesters, but says he never killed anyone.
A British report said that McGuinness probably was armed with a submachinegun on Bloody Sunday, but did nothing to provoke the massacre. He has said he left the IRA in 1974, but most historians believe he was active for most of its campaign.
For the queen, the Northern Ireland conflict has long had a personal edge. Her cousin Lord Mountbatten was killed in an IRA attack in 1979 with three others, including his 14-year-old grandson, when his boat was blown up while he was on holiday in the Irish Republic. More than 1,000 members of the British security forces were among 3,600 killed during the 30 years of violence.
"I represent people that have been terribly hurt by British state violence over the course of many years," McGuinness said in a video interview that Irish journalist Eamonn Mallie posted on his website on Tuesday.
"But I am also big enough to understand that Queen Elizabeth has also lost a loved one and of course there are families in Britain. Mothers, fathers, sisters and brothers, children of people who were sent here as British soldiers who lost their lives also," he said.
Sinn Fein, which has become increasingly popular south of the Irish border as the main party opposing an EU/IMF bailout that the republic needed when its property bubble burst, is keen to bolster its image as a mainstream party and distance itself from a violent past that alienates many southern voters.
Sinn Fein still wants a referendum on whether Northern Ireland should remain part of Britain, where its members still refuse to take their parliamentary seats, but in the short term its aim is to be in government north and south simultaneously.
Just last year Sinn Fein rejected invitations to attend events during the queen's symbolic visit to the Republic of Ireland last year, the first by a British monarch since Dublin won independence from London in 1921.
"I see this as an opportunity to give the Unionist people in the north a glimpse of what a united Ireland can look like and their role in it and how they can be accommodated," McGuinness said. "This is about deciding at a moment in history what is the right thing to do."
The simple announcement of the trip in advance, for the first time since the conflict began, shows the vast progress the province has made in recent years.
When the queen last visited for a jubilee celebration in 1977 she was forced to stay overnight on a ship at sea before flying to Belfast, parts of which were effectively controlled by the IRA.
Security remains tight with small splinter groups continuing to launch attacks against British targets, a threat the police say it at its highest level since peace in 1998.