Karyotypic analysis by direct demonstration of DNA sequences in interphase nuclei has been termed interphase cytogenetics and can be applied to a wide variety of cellular material, including paraffin-embedded tissue, allowing detection of both numerical and structural chromosome aberrations. The principal established method is the fluorescence in situ hybridization (FISH) technique, but more recently primed in situ labelling (PRINS) has been employed, as illustrated in an accompanying paper in this issue of the Journal. Where there are defining cytogenetic abnormalities, as is the case for the detection of fetal numerical chromosome abnormalities and in some paediatric and soft tissue tumours, this approach has clear diagnostic applicability. In other circumstances, such as the investigation of most solid tumours, this technique is largely of research interest but, particularly with application to paraffin sections, is providing valuable information on the morphological distribution of molecular changes in both invastive and 'pre-invasive' lesions. Continued technical refinement and research application of this methodology will lead not only to greater clinical applicability but also to improved understanding of the pathobiology of tumours.