The thymidylate synthase (TYMS) gene expression was analysed by Northern-blotting and by reflectance in situ hybridization (RISH) in human histological colorectal cancer. Scattering reflectance signals from 1-nm colloidal-gold particles after in situ hybridization, using digoxigenin-labeled probe, were quantified by confocal scanning laser microscopy. The importance of the RISH method is demonstrated by results obtained on colorectal cancer specimens. This study demonstrates a quantitative difference between cancer cells and normal colon epithelial cells in situ. In addition, TYMS expression varies from turner to tumor, in relation with karyotypic patterns. When the number of copies of chromosome 18, which carries the TYMS gene, are considered, there is a significant correlation with TYMS mRNA amounts, suggesting the existence of a gene dosage effect in colorectal cancer cells.