Clonality testing is a mature technique that is a reliable toolin the routine diagnostics of lymphoproliferations [1].Almost all lymphomas are clonal [2, 3], and the majority ofreactivelymphoproliferationsarepolyclonal[4].Althoughthestandard method, using the full program of antigen receptors,is now available for almost a decade [5], there is still greatneed for teaching and exchange of experience. This is due tothe fundamental different principles that form the basis ofclonality testing as a molecular test, compared to other mo-lecular tests in pathology. Most molecular tests deal with apathological change in the DNA of a tumor. Examples are ofcourse mutations and amplifications in oncogenes, transloca-tions resulting in abnormal gene activity or even novel pro-teins. In all these situations, there are important quality issuesand external quality assurance is mandatory [6–8]. In thesetests the interaction of pathologists and molecular biologistsshouldnotbeunderestimated,but it isnot incomparisonwithclonality testing. The main reason is that clonality testing isnotdealingwithpathologicalbutratherphysiologicalchangesin the DNA.It is well known that every mature B and T cell has aunique set of rearranged antigen receptor genes, unique inthe sense that after a B or Tcell is fully differentiated, it willstart to proliferate in case the proper antigen is presentresulting in small clones. The usefulness of clonality testinglies in the fact that reactive lesions have proliferations ofmany different B and/or Tcells, whereas a malignant lesionconsists of the proliferation of a single B or T cell. It istherefore clear that in principle, a sensitive clonality test, inwhich rearranged antigen receptors are amplified, will detectevery B and T cell, physiological or pathological. A sharpcontrast with a test which aims at the detection of a patho-logical change: in case a mutation is found, it implies thatthe test is positive. In case a clonal B or Tcell population isfound, it implies only that there is indeed a clonal popula-tion. This result really has to be interpreted in the fullpathological context of the lesion. And this can only bedone by bringing the pathology (morphology and immuno-phenotype) and molecular biology together.This special issue on clonality testing in Hematopathologyassemblesaseriesofarticlesthatdealwithproblematicissuesin applying this test and thus really is a teaching issue. In thiseditorialsomeoftheseissuesareoutlinedstressingtheimpor-tance of the interaction of the molecular biologists and thepathologists, each with her or his own expertise.In general, a pathologist orders clonality testing in case alesion is not clearly malignant or reactive. Some patholo-gists order clonality testing to confirm their diagnosis of alymphoma. In such cases one may expect a relativelystraightforward result of a clonality test: a dominant clonalresult with a small background polyclonal pattern. Althoughthis is helpful for building up experience, it is likely notcost-effective. In the more problematic cases, there can bemultiple clones and one of these may be malignant. Onetherefore needs to combine all data to come to a conclusion.Here we discuss some situations in which the interactionis critical.– The composition of the tissue tested is important forinterpretation of the clonality results. Normal germinalcenters consist of one or a few B cells that are in the