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Hereditary non-polyposis colorectal cancer (HNPCC) helps us understand how medical genetics has changed over the last forty years. The concept of the "cancer family" emerged from the realization that members of some families developed cancer more frequently than members of others, which led to a series of strategies by clinicians in the 1960s to persuade others of this. By the early 1990s molecular genetics had transformed the disease, from one that a few physicians believed ran in families, to one with precise genetic components that researchers generally accepted, and that could be detected through genetic tests. Nevertheless, a diagnosis of HNPCC still requires that the mutated genes be found within a kin group that is generally accepted as a cancer family. Moreover, the "cancer family" construct was crucial in the search for the HNPCC genes. HNPCC's trajectory can be mapped onto important debates about the complex relations between clinical and molecular genetics knowledge and practice.