Baroness Warsi has quit the government, saying she can no longer support its policy towards Gaza.
The senior minister for Foreign and Commonwealth affairs and for faith and communities tweeted her resignation this morning.
i100 believes this is the first time a government figure has quit, not just in the UK, but also in the EU or the US, in protest over policies regarding Israel and Gaza.
Her resignation follows prime minister David Cameron refusing to condemn an alleged Israeli strike upon a United Nations school as "criminal".
This led to recriminations between No 10 and Labour when Ed Miliband rebuked Mr Cameron for his "silence on the killing of innocent Palestinian civilians", while Downing Street accused Mr Miliband of playing politics.
In her resignation letter, Baroness Warsi strongly hints that Israel may have committed war crimes, and suggests the removal of attorney general Dominic Grieve and Ken Clarke from the Cabinet in the last reshuffle may have contributed to the government's line on Israel's actions.
Baroness Warsi was first appointed to the Cabinet after the last general election. She was demoted to a middle-ranking Foreign Office post two years on but still attended Cabinet meetings.
Some people have suggested the resignation had more to do with internal politics than international issues.
There was also a very short-lived suggestion from former Tory whip Mike Fabricant that Baroness Warsi's Muslim faith was central to her decision.
World War One commemoration services yesterday most likely delayed Baroness Warsi's resignation by at least one day, meaning the news of her stepping down coincides with the start of a 72-hour ceasefire in Gaza that has, so far, been observed by both sides.
Her resignation plus the mounting death-toll (1,800 Palestinians and 67 Israelis) could lead to calls for Parliament to be recalled during the summer recess.
It has also certainly put the government's response to Israel's military operations in the Gaza Strip in even sharper focus than they already were, and partly vindicated Mr Miliband's stand against the prime minister.
The Prime Minister regrets that Baroness Warsi has decided to stand down and is grateful for the excellent work that she has done both as a Minister and in Opposition.
Our policy has always been consistently clear - the situation in Gaza is intolerable and we've urged both sides to agree to an immediate and unconditional ceasefire.
But its wider impact is questionable.
What this most recent stage of the Israeli-Hamas conflict has shown is that Israel is not easily swayed by even its closest ally the US condemning its actions when civilians are killed.
An arms embargo against Israel remains as distant a possibility as it did before the war in Gaza began.