As was shown in the first two volumes of this series, great strides have been made in identifying many of the agents or classes of substances responsible for carcinogenesis and in delineating their interactions with the cell. Clearly, the aim of such studies is that, once identified, these agents can be eliminated from the environment. Yet, despite these advances and the elimination of some important carcinogenic agents, one major problem exists. It is a constant monitor of all oncologic study and diminishes the importance of every experiment and of every clinical observation. As we noted earlier, that problem is our inability to define the malignant cell. It is through studies of the fundamental biology of tumors that we seek this definition. A vast amount of information has been gathered which describes what this cell does and-to a lesser extent-how it does it. But the why evades us. We have been unable to define the malignant cell, save in broad terms by comparing it to its normal counterpart. The major problem appears to be that the malignant cell does so much. It is a chimera, mystifyingly composed of normal activities and structures, of phenotypic schizophrenia with embryonic, fetal, and adult charac­ teristics and, occasionally, a hint of an unclassifiable capacity unique to malignant cells.