The monocyte-specific (carboxyl)esterase (MSE) is a marker enzyme which is well-known to hematologists as its detection is part of the traditional cytochemical stainings of leukemia cells. There are a variety of synonyms for MSE among hematologists and biochemists. Biochemically, MSE is well-characterized, but should be discerned from other esterases with similar or identical substrate specificities and other features. Intensive analysis of normal and malignant hematopoietic cells and leukemia-lymphoma cell lines using isoelectric focusing established the specificity of this enzyme for monocytes and related cells, hence its designation as monocyte-specific esterase. Cloning of the gene led to its molecular characterization and provided new opportunities to examine MSE expression also at the RNA level which confirmed the monocyte/macrophage specificity. The availability of the gene sequences of various serine esterases and lipases which also hydrolyze ester bonds allowed for the identification of identical isolates from different tissues and the construction of an unrooted dendrogram based on sequence homologies of 22 enzymes. The detailed regulation of the gene and the functional role of MSE have remained largely unknown as of yet. However, DNA binding sites for various transcription factors have already been detected. Some evidence suggests involvement in physiological detoxification processes and in the immune defense against tumor cells. A more thorough understanding of the in vivo function of this truly unique enzyme should be helped by characterizing the signals and signal transduction mechanisms which lead to MSE expression.