Former deputy prime minister Lord Heseltine says an "ill-advised" referendum on Europe would jeopardise the UK's business prospects.
The former minister - known for his Europhile views - said the prime minister would be taking a "punt" by offering a national vote before negotiations about the EU's future shape have started.
The comments came in interviews with The Times and Financial Times, ahead of an anticipated speech by Mr Cameron on the union later this month.
Lord Heseltine, an adviser to the coalition on economic growth, insisted: "Mrs Thatcher said 'Never go into a room unless you know how to get out of it'.
"To commit to a referendum about a negotiation that hasn't begun, on a timescale you cannot predict, on an outcome that's unknown, where Britain's appeal as an inward investment market would be the centre of the debate, seems to me like an unnecessary gamble."
He added: "If I was responsible for inward investment into any of our European colleagues, it would give me the best argument I could dream of.
"Why put your factory (in Britain) when you don't know - and they can't tell you - the terms upon which you will trade with us in future?"
Mr Cameron is under intense pressure to offer an in-out referendum on Britain's membership of the EU when he unveils his approach in the coming weeks.
Tory big beast Lord Heseltine has previously said he still believes the UK will join the euro in the end.
11 January 2013
07 January 2013
31 October 2012