Development of the oral and craniofacial region is a complex and fascinating set of processes which require a sequential integration of numerous biological steps. For medical and dental doctors, interest is particularly high in this region, because it is composed of three blastoderms - ectoderm, mesoderm, and endoderm - as well as neural crest cells. There are many different types of neoplasms in this region. In general, proliferation, development and cytological differentiation of the neoplastic cells reflect the normal physiological development of the outbreak mother cells and/or tissues. Collected human neoplasm cases, such as osteosarcoma appearing in the oral and craniofacial region, are examined regarding the immunohistochemical expression of some morphogenesis regulation factors. Furthermore, examination of Notch signaling is also conducted for some odontogenic neoplasms. This chapter mainly describes the examination results of some morphogenesis regulation factors, such as Notch signaling, in the neoplastic cells originating in the oral and craniofacial region, especially in the odontogenic neoplasms, in both well-differentiated and poorly-differentiated neoplasms of tooth germ enamel organ-derived neoplasm. In general, these morphogenesis regulation factors are responsible for cytological regulation of cell fate, morphogenesis and/or development. The results suggest that these factors play some role in cytological differentiation or acquisition of tissue specific characteristics in neoplastic cells. Furthermore, there would appear to be a relationship between the cytological differentiation in the oral and craniofacial neoplastic cells and the physiological development and differentiation of their originating mother cells and tissues of the oral and craniofacial region. © 2007 by Nova Science Publishers, Inc. All rights reserved.