One of the country's biggest exam boards, OCR, has admitted to an error in Friday's English Literature GCSE exam, taken by around 14,000 teenagers.
The mistake related to a question on Shakespeare's Romeo and Juliet in which the family background of a key character, Tybalt, was mixed up.
It suggested he is a Montague when in fact he is a Capulet.
The board apologised and said no candidates would lose out, but head teachers said the error was "serious".
Exams regulator, Ofqual, said the incident was unacceptable and that it would be "closely monitoring OCR's investigation of how this incident occurred".
Geoff Barton, general secretary of the Association of School and College Leaders, said when candidates see errors in a paper it can undermine their confidence.
He added: "Candidates have every right to expect that awarding bodies complete a full check on exam papers to ensure that they don't experience such problems.
"Similarly, schools and colleges have to pay thousands of pounds a year to examination boards and are entitled to better quality assurance than this.
"This appears to be a serious error and it will have caused stress and concern to candidates."
However, some students reacting to the exam on Twitter said that they had wasted time on the question, while teachers also spoke out.
One pupil, Sophie Elder, 16, from Derbyshire, said: "I got to the question, I read it, and read it again and thought that doesn't make sense.
"It really threw me off - it had been fine until then, and then this happened."
She added: "We had all tried so hard and made so much effort, and then for the board to mess it up, it's just terrible.
"It's so distracting - afterwards everybody was so worried and stressed that they had got it wrong. You don't expect something like that on your exam."
OCR said about 14,000 students out of around 700,000 took the exam, but it is not clear how many tackled the question, which asked students: "How does Shakespeare present the ways in which Tybalt's hatred of the Capulets influences the outcome of the play? Refer to this extract from Act 1 Scene 5 and elsewhere in the play."
In a statement, the exam board said: "We're aware of an error in today's OCR GCSE English Literature paper.
"We apologise and will put things right when the exam is marked and graded so no student need worry about being disadvantaged. We are investigating as a matter of urgency how this got through our assurance processes."
Russell Hobby, general secretary of school leaders' union NAHT, said: "After two years of study it's not acceptable for students to face such a basic error in their exam papers.
"OCR are rightly apologetic but just exactly how they propose to mark this particular paper will leave many students, their schools and their parents with an anxious wait for their results.
"OCR need to be particularly open to any requests for a re-mark if students feel that their efforts have not been properly graded."
Ofqual added: "We will be scrutinising how OCR intends to identify and minimise the impact on these students. We will be closely monitoring OCR's investigation of how this incident occurred and seeking reassurance regarding its other papers this summer."