  What is cancer? Is cancer one disease, or many? If many, how many cancers are there? One might think that such questions are merely empirical. However, it turns out that defining and classifying cancer is contested, for at least two reasons. First, there is little agreement on how to classify disease, more generally. Second, cancer itself poses a variety of challenges—both in terms of its intrinsic heterogeneity, and in light of its variable natural history. In section 1.1, we will consider challenges facing cancer classification in light of cancer’s intrinsic heterogeneity, and in section 1.2, we will consider challenges facing cancer classification in light of its variable natural history.