We seek to start a dialogue about the challenges cancer control researchers and specialists may face in attempting to understand the Appalachians' experience with cancer. Through examples drawn from our own research among Appalachian communities, we discuss the hazards of defining a culture in order to develop culturally tailored cancer control interventions and programs. We also acknowledge that cancer control work in Appalachia requires "cultural mapping," highlighting cultural beliefs, norms, and realities that may be linked to cancer mortality and morbidity. Although cancer control specialists and researchers have to rely on cultural maps, they must also remain critical of such maps. Subsequently, we describe a mapping approach around the metaphor of "signposts," directional indicators that point to broad cultural attributes but do not reduce the culture to a narrow set of traits. The interplay of these signposts ultimately helps cancer educators, communicators, and researchers better understand authentic Appalachia.