The techniques for obtaining chromosomes from phytohemagglutinin (PHA)-stimulated lymphocytes for constitutional studies have been standardized to give consistent, reproducible results in almost all cases. It is therefore possible to refine and define a protocol that can be confidently used to provide an abundance of high-quality metaphases and prometaphases. For malignant cells, however, it can seem that every patient’s chromosomes have an idiosyncratic reaction to the culture conditions, if the abnormal cells condescend to divide at all. For example, samples from different patients with leukemia can give widely different chromosome morphologies, even when processed simultaneously. In some cases it is also possible to recognize distinct populations of divisions on the same slide, often those with good morphology being apparently normal and those with poor morphology having some abnormality. It was once thought that poor morphology alone, even in the absence of detectable abnormality, might be sufficient to identify a malignant clone. However tempting this explanation has been to anyone who has seen such coexisting populations, such a hypothesis has not been subsequently confirmed. The formal demonstration of a clone in malignancy still requires the identification of some acquired genetic abnormality.