The TNM Classification describes the anatomic extent of cancer. TNM's ability to separately classify the individual tumor (T), node (N), and metastasis (M) elements and then group them into stages differs from other cancer staging classifications (e.g., Dukes), which are only concerned with summarized groups. The objectives of the TNM Classification are to aid the clinician in the planning of treatment, give some indication of prognosis, assist in the evaluation of the results of treatment, and facilitate the exchange of information. During the past 50 years, the TNM system has evolved under the influence of advances in diagnosis and treatment. Radiographic imaging (e.g., endoscopic ultrasound for the depth of invasion of esophageal and rectal tumors) has improved the accuracy of the clinical T, N, and M classifications. Advances in treatment have necessitated more detail in some T4 categories. Developments in multimodality therapy have increased the importance of the "y" symbol and the R (residual tumor) classification. New surgical techniques have resulted in the elaboration of the sentinel node (sn) symbol. The use of immunohistochemistry has resulted in the classification of isolated tumor cells and their distinction from micrometastasis. The most important challenge facing users of the TNM Classification is how it should interface with the large number of non-anatomic prognostic factors that are currently in use or under study. As non-anatomic prognostic factors become widely used, the TNM system provides an inviting foundation upon which to build a prognostic classification; however, this carries a risk that the system will be overwhelmed by a variety of prognostic data. An anatomic extent-of-disease classification is needed to aid practitioners in selecting the initial therapeutic approach, stratifying patients for therapeutic studies, evaluating non-anatomic prognostic factors at specific anatomic stages, comparing the weight of non-anatomic factors with extent of disease, and communicating the extent of disease data in a uniform manner. Methods are needed to express the overall prognosis without losing the vital anatomic content of TNM. These methods should be able to integrate multiple prognostic factors, including TNM, while permitting the TNM system to remain intact and distinct. This article discusses examples of such approaches.