The BIOMED-2 group developed and approved a set of multiplex Ig and T cell receptor PCR primers and successfully applied these to different well-defined WHO lymphoma entities with unprecedented high frequencies of malignant cases showing clonality. This approach has now become a worldwide standard of clonality testing in lymphoproliferations. While the clonality testing and assessment by GeneScan and/or heteroduplex analysis has become relatively easy to perform, the evaluation of the obtained gene rearrangement patterns can be difficult. In this review, we will address specific aspects of clonality testing, concerning both the practical phase as the evaluation of the obtained gene rearrangement patterns, which will help to overcome problems that can be encountered in the routine diagnostic setting.