Molecular studies on whole samples of fresh or frozen tissue do not take into account the heterogeneity of these tissues. In addition to normal cells, precursor lesions and different progression stages may be mixed within a given sample. Usually, the dominant cell population will determine the results and may sometimes mask biologically relevant abnormalities. To obtain more specific information and knowledge on changes within different cell compartments, many techniques have been developed that combine morphological observation and selection with different strategies for specific cell dissection. In this review, the most important micro-dissection methods are put into perspective, and some requirements and limitations are discussed with regard to sample fixation, staining, dissection and molecular analysis.