The categorization of variables can stigmatize populations, which is ethically problematic and threatens the central purpose of public health: to improve population health and reduce health inequities. How social variables (e.g., behavioral risks for HIV) are categorized can reinforce stigma and cause unintended harms to the populations practitioners and researchers strive to serve. Although debates about the validity or ethical consequences of epidemiological variables are familiar for specific variables (e.g., ethnicity), these issues apply more widely. We argue that these tensions and debates regarding epidemiological variables should be analyzed simultaneously as ethical and epistemic challenges. We describe a framework derived from the philosophy of science that may be usefully applied to public health, and we illustrate its application. (Am J Public Health. Published online ahead of print November 13, 2014: e1-e7. doi:10.2105/AJPH.2014.302279).