Development of the tooth is a complex and fascinating set of processes which require a sequential integration of numerous biological steps. For dental doctors, interest is particularly high, because the tooth is mainly composed of surface ectodermal epithelium and neural crest derived neuroectodermal mesenchyma, and formed by epithelial-mesenchymal interactions. There are many different types of odontogenic neoplasms. In general, proliferation, development and cytological differentiation of the neoplastic cells reflect the normal physiological development of the outbreak mother cells and/or tissues. There would appear to be a relationship between the cytological differentiation of odontogenic neoplastic cells and the physiological development and differentiation of tooth germ. We describe some morphogenesis regulation factors, such as Notch signaling, in the odontogenic neoplastic cells, in both well-differentiated and poorly-differentiated neoplasms. Our results suggest that these factors play some role in cytological differentiation or acquisition of tissue-specific characteristics in neoplastic cells. © 2008 The Hard Tissue Biology Network Association Printed in Japan, All rights reserved.