In a continually renewing cell population, stem cells can be regarded as a reservoir of cells with a high capacity for self renewal that give rise to all differentiated progeny. They are the primary source for the generation and maintenance of cellular diversity and tissue homeostasis. In general, neoplasms manifest differentiation pathways similar to those found in the development and renewal of the normal tissues from which they arise. This feature serves as a basis for classification schemes of neoplasms and, as in the normal tissues, there is usually an inverse correlation between proliferative capacity and differentiation within the neoplasms. In our postulate of the histogenesis of salivary gland neoplasia, we evoke the stem cell model to account for the considerable phenotypic heterogeneity seen with these neoplasms. We further consider the neoplasms and, in particular, their myoepithelial constituencies to be manifestations of escape from normal regulatory mechanisms that determine differentiation pathways which a stem cell and its progeny can take. Clinical and basic scientific evidence are presented to support the postulate and also to point to the mitigating role that myoepithelial differentiation has in the biological course of salivary gland neoplasms.