Background: Elevated alphafetoprotein (AFP) concentrations may result from a variety of clinical conditions, but their role as an important tumour marker has been well established. There may be differences in AFP values due to laboratories using different methods, even though most methods have been calibrated with the same international standard (WHO IS 72/225). Therefore it is important to know the analytical performance of the various methods in relation to the analytical requirements for AFP measurement. Methods: Annually, from January 2005 to July 2010, the results were analysed from the 65-75 laboratories that took part in the AFP survey of the External Quality Assurance programme of the Foundation Quality Control Medical Laboratories (the SKML/ Binding Analysis) in the Netherlands. Results: The Elecsys/Modular (36%) and the Immulite 2000/2500 (29%) are the methods used most. The methods show, on average, up to 15% positive and 12% negative bias, compared with the all-laboratory trimmed mean. Of the laboratories using the Immulite or the Elecsys/Modular analyser, over 70% show sufficient analytical performance to meet the Fraser criterion for method imprecision. Of the laboratories using a different method, over 50% do not meet this criterion. Conclusions: AFP immunoassays suffer from method bias, even though all methods have been calibrated with the same international standard. Some of the methods used show insufficient performance.