DNA analysis by quantitative cytochemistry has been a widely exploited approach to investigate chromatin superstructural changes in relation to cell function and cell cycle progress. To this aim, a number of dyes (especially fluorochromes) for nucleic acids have been used, exhibiting different peculiarities, in terms of both binding mechanism and base specificity. Less attention has been paid to the application of different DNA staining techniques for studying possible differences in genome organization among different taxa. The purpose of this paper is to review and discuss the present reports in the literature, concerning the cytochemical analysis of genome organization, in a comparative perspective. Special attention is given to the integration of quantitative studies based on cytofluorometric and imaging techniques.