Head teachers say thousands of pupils could miss out on expected GCSE grades because of "significant turbulence" in this year's results.
As changes to make core GCSE subjects harder begin to bite, heads warn grades are becoming unreliable and incomparable year on year.
So much so that many pupils predicted to get grade C in core subjects may not now achieve it, they say.
Exams regulator Ofqual says "standards will be maintained" despite changes.
Pupils in England, Wales and Northern Ireland will be receiving their GCSE results on Thursday.
The Ofqual exam watchdog in England has already warned that GCSE English, maths and all science results are likely to "look different" with grades possibly dropping this year because of changes to the exams and the patterns of entry.
The Association of School and College Leaders, which represents thousands of secondary school heads, said it was expecting "significant turbulence" in this year's results.
Its general secretary Brian Lightman said that the exam system was in a very "serious state" and he called for "some stability".
It was no longer possible to assume that children taking the same subject years apart would get the same grade for the same standard of work, he said. And those who had achieved similar standards may be graded differently, he added.
The organisation's vice-president Ian Bauckham, who is also a head teacher in Kent, said there was a significant level of anxiety over the changes in the core subjects this year.
"It is likely that some pupils whose teacher thought they were on track to get a grade C in these core subjects may well find they have fallen below the new boundary where grade boundaries have been changed."
Many schools focus efforts on C-D borderline pupils because obtaining a C grade in English and maths is the key academic requirement for pupils to continue in education, whether it be studying A-levels or a more vocational course. These grades are also the key measure of accountability for schools.
General secretary of the National Association of Head Teachers Russell Hobby said: "The exam system is so massively complicated now, I actually think it is beyond any organisation's capability to keep it under control."
The exams regulator's crackdown on grade inflation, through the system known as comparable outcomes, had led to Ofqual "regulating the exam system through the rear view mirror," he said.
This was wrong, he added, "we need to be doing it beforehand."
Under comparable outcomes, the regulator ensures that roughly the same proportion of students achieve each grade as in the previous year.
But alongside this, statistical predictions based on the results of national primary school tests sat by the candidates, and chief examiner judgments, are used to set the grade boundaries.
Mr Hobby said: "A lot of us assumed that there was more objectivity to the grades people get. Exams are often held up as being this objective standard, but there's a lot of subjectivity in the marking and grading of exams. It's quite shocking."
But Mr Lightman said: "There is a recognition that so much instability in the system means the people who need to know will have much more difficulty in interpreting the data.
"It's going to be very difficult for universities, for employers, for parents and students to understand when the exam system is going through this constant change, and there are more changes down the line."
He added: "There needs to be a transparent link between what young people are expected to know or be able to do and the result they end up with, and that results should not be calculated - especially at GCSE - in the back room using statistical methods which distance results from clarity about what the grades actually mean.
"When the government make changes to complex things like qualifications that are not fully thought through, then you end up with unintended consequences."
Dr Mary Bousted general secretary of the Association of Teachers and Lecturers said: "There have been changes this year to some GCSE science subjects which will be awarded for the first time.
"We know that these new GCSEs have been designed to be more challenging, and that there may be a drop in achievement overall, but we hope this doesn't cause disappointment to students."
Glenys Stacey, chief exams regulator, said Ofqual's main role was ensuring that exam standards were set and maintained and this was what they were doing.
"We want to make sure that whatever exam board you are sitting that you will get the right results."
She insisted that pupils would be getting the correct grades, and added: "When we look at the national results and see some changes - the very reason for that is because we have maintained the standards."
Professor of Education at Buckingham University Alan Smithers said grades were becoming more "believable" because of the changes the government and Ofqual had made.
He said: "If you have been measuring foot sizes inaccurately for a number of years then you get shoes which don't really fit. When you discover ways of making the measuring more accurate it makes good sense to make use of the more accurate measure."
A Department for Education spokesman said: "We want GCSEs to be high-quality, demanding qualifications comparable to those in the world's best-performing education systems.
"It is for Ofqual, the independent regulator, to ensure that standards are set appropriately in the awarding of GCSEs."