The major focus of cancer immunology has shifted away from arguments about the validity of the immunosurveillance theory of cancer to the more basic question of tumor-specific antigens. Despite vast effort aimed at demonstrating such antigens, their existence in the generality of cancer remains unproven. Serological analysis of three tumor types, mouse leukemia, mouse sarcoma, and human malignant melanoma, has received most attention, and a rudimentary classification of the surface antigens expressed by these tumors has begun to emerge. The prime candidates for antigens that can be considered tumor specific are the few instances of Class 1 antigens that have now been serologically defined on mouse and human tumors. These antigens show an absolute restriction to individual tumors, not being demonstrable on any other normal or malignant cell type. Biochemical and genetic characterization of Class 1 antigens represents an essential next step in evaluating the significance of these antigens. The surprising features of the Thymus Leukemia (TL) antigens of the mouse provide insight into the genetic origin of another key class of tumor antigens, in this case antigens with characteristic properties of both differentiation antigens and tumor-specific antigens. In normal mice, TL antigens are restricted to cells in the thymus, and strains differ with regard to expression versus nonexpression of TL antigens. Genetic information for TL is universal in the mouse, however, as leukemias developing in mice that normally lack TL are found to express TL. What is clear from the past two decades of research in cancer immunology is that a far more detailed knowledge of surface antigens of tumor cells will be necessary before we can begin to assess the possibility of immunological control of cancer.