The scale of the Tory rebellion on the EU referendum - it looks like 81 MPs - has implications for the constitutional future of Scotland too.
With almost half the Tory backbencher who are not hired as ministers or bag carriers openly defying him, Cameron has entered the nightmare territory for any Conservative leader.
The Tory Party's ability to tear itself apart over Britain's role in Europe is well-remembered, not least by Cameron who as a party researcher had a front-row seat on the "bastards" vs John Major over Europe in the 1990s.
This time it's different - a highly Eurosceptic Tory party and a leader who over-promised the rightwingers on his path to power.
In the next few years Cameron could be wrenched by either arm on the constitutional questions as Salmond on one side, and his own Eurosceptics on the other, try to tear up the UK settlement.
Tonight's Westminster rebellion on the EU must now limit Cameron’s room for maneouvere on Scotland. Downing Street has been mulling over whether to call its own early referendum on Scotland’s future in the UK.
The PM is said to be open-minded on whether to order a simple Yes-No referendum on Scottish independence ahead of Alex Salmond’s plans for a multi-option ballot sometime beyond 2014.
But to call a referendum on one constitutional issue while denying his own backbenchers a vote on another will prove highly tricky.