Andrew Lansley should be sacked as health secretary once his controversial health reforms have been passed by parliament, Liberal Democrat deputy leader Simon Hughes has said.
On Sunday David Cameron used an article to insist he was "at one" with Lansley and backed the controversial NHS reforms going through parliament.
A series of senior Tories were also deployed to television studios in a bid to shore up the Cabinet minister's position.
However, Hughes broke ranks to demand Lansley be shifted from his post.
"My political judgment is that in the second half of the parliament it would be better to move on," he told the BBC's Andrew Marr show.
Several Conservative cabinet ministers are said to have privately criticised Lansley's handling of the Health and Social Care Bill, with one suggesting the government's problems were now on the scale of the Poll Tax in the 1980s.
A Downing Street source was also quoted last week saying that the health secretary should be "taken out and shot".
However, writing in The Sunday Times,Cameron stressed that there was no alternative to reform.
Labour's shadow health secretary Andy Burnham said that Cameron was "putting his political pride before the best interests of the National Health Service".
"The Tory-led government seems to be in meltdown over the Health Bill," he said.
"Not only do we have senior Tory Cabinet ministers calling if for it be dropped, we also have senior Liberal Democrats calling for the removal of the Health Secretary on national television."