Histone deacetylases are known to play a central role in the regulation of several cellular properties intimately interlinked with the development and progression of cancer. Consequently, a multitude of histone deacetylase (HDAC) inhibitors have been developed and are currently tested as anticancer agents in a variety of solid and hematologic malignancies. However, only recently research began to focus on the actual expression patterns of specific HDAC isoforms in neoplasias. The majority of studies investigating this issue reported an enhanced expression of class I HDAC isoforms in solid human tumours, both on mRNA and protein level, when compared to the respective tissue of origin. In most studies, class I HDAC expression was high in locally advanced, dedifferentiated, strongly proliferating tumours. In some but not all entities elevated class I HDAC expression was associated with compromised patient prognosis, however, an association of elevated class I HDAC expression with improved prognosis has also be reported for selected tumour entities. In contrast to class I isoforms, expression of class II HDACs has been found reduced in tumours and high expression of these isoforms in some entities predicted better patient outcome. Since all of these data point to a potential biological role of differences in HDAC expression in human tumours, future translational studies will focus on the question, whether HDAC expression patterns are predictive for response to treatment with histone deacetylase inhibitors.