The former Conservative Chancellor, Lord Lawson, has significantly widened the deep fracture within the Tory party over the toxic issue of Europe.
In an explosive intervention he piled the pressure on the Prime Minister saying it was time to quit the EU and any concessions Mr Cameron could negotiate would be 'negligible'.
ITV News political editor Tom Bradby reports:
Lord Lawson became the most senior Tory figure to call for the UK to quit the European Union - pledging to vote No in any referendum on membership.
In a move that piles further pressure on David Cameron over the issue, the former chancellor warned the Prime Minister's proposed renegotiation would only secure "inconsequential" concessions from Brussels.
Writing in The Times (£), he said there was now a "clear" case for withdrawal, insisting the economic benefits would "substantially outweigh the costs", in contrast to the Prime Minister's position.
His intervention is sure to further embolden eurosceptic MPs demanding a tougher line to halt the rise of Nigel Farage's rampant anti-EU UK Independence Party (Ukip).
Mr Cameron is already under pressure to hold a "mandate referendum" as early as next spring to seek public approval of his strategy of putting a renegotiated settlement to an in/out vote by 2017.
In the wake of Ukip's surge in last week's county council elections, there is also pressure to put the strategy to a vote in the Commons in defiance of his Liberal Democrat coalition partners.
Lord Lawson, who was Margaret Thatcher's longest-serving chancellor and remains a highly-respected figure within the party, said that it was "by no means assured" that Mr Cameron would win the 2015 general election.
But he said he believed public demand was such that a referendum would have to happen under Labour in any case.
Dismissing the chances of either party securing significant reforms, he said Brussels would fear a "general unravelling" as other countries sought to match the return of powers.
– Lord Lawson writing in The Times
But all this is largely beside the point.
The heart of the matter is that the very nature of the European Union, and of this country's relationship with it, has fundamentally changed after the coming into being of the European monetary union and the creation of the eurozone, of which - quite rightly - we are not a part.
That is why, while I voted 'in' in 1975, I shall be voting 'out' in 2017.
Not only do our interests increasingly differ from those of the eurozone members but, while never 'at the heart of Europe' (as our political leaders have from time to time foolishly claimed), we are now becoming increasingly marginalised as we are doomed to being consistently outvoted by the eurozone bloc.
So the case for exit is clear.
While there would be "some economic cost" from leaving the EU single market, he went on, "in my judgment the economic gains would substantially outweigh the costs.
– An excerpt from the article Nigel Lawson wrote in The Times
The Bank of England is becoming increasingly frustrated by the mandatory nonsense emanating from Brussels
Escaping from this and reinforcing the escape by co-operation with the only other genuine world financial centre, the United States, would be a major economic plus.
Those who claim that to leave the EU would damage the City are the very same as those who in the past confidently predicted, with a classic failure of understanding, that the City would be gravely damaged if the UK failed to adopt the Euro as its currency.
Quitting the single market would only have "marginal" disadvantages, he suggested, and could even have "a positive economic advantage to the UK" by forcing British firms to look further afield.
Too much UK business and industry felt "secure in the warm embrace of the European single market and is failing to recognise that today's great export opportunities lie in the developing world", the peer wrote.
Richard Edgar reports on how the issue is dividing British businesses: