In the past several decades, concepts of neoplasia have changed markedly. Research efforts in a number of systems including colorectal cancer, cervical cancer, melanoma, and experimental systems in animals such as hepatoma have generated a large body of information on neoplastic development.1–7 Neoplasia appears to be a chronic process that develops through a series of progressive stages, sequentially acquiring various biologic features associated with “malignant” behavior. Although these features are relatively well characterized morphologically in a few systems such as melanoma, cervical carcinoma, and colorectal carcinoma, in most tumor types, the sequence of morphologic changes that comprises the neoplastic developmental pathway is poorly or incompletely characterized. In addition, the differences between various stages of neoplastic development are very poorly understood at a basic molecular level. Nonetheless, several generalizations are important to consider: