The problems of using tissue disaggregation techniques or less than stringent microdissection techniques in the determination of tissue clonality: (a) human colon from an XO/XY mosaic, with NISH demonstration of nuclei containing the Y chromosome. Myofibroblasts which are very closely applied to the epithelium show a different clonal origin; (b) white blood cells, shown red by immunohistochemistry with an antibody against leukocyte common antigen, are present between crypt epithelial cells, and are the source of Y-positive nuclei in an otherwise negative crypt, and (c) a tubular adenoma from the same individual showing a normal, negative crypt in a Y-chromosome positive adenoma, showing how easy it is to include normal tissue in a neoplastic lesion (from Novelli et al. 1996, with permission).