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How do we make a difference? This paper traces the connections made between quantified knowledge, population health, and social justice by examining the efforts of population scientists to assess sexuality as a point of difference within population-based data systems, including on national health and social surveys, electronic medical records, and the Census. Population scientists emphasize the importance of measuring social difference in order to identify and remedy structural disadvantage. This evaluation requires the assessment of difference and the comparison of distinct groups against standardized outcome measures. In quantifying social difference, however, population scientists obscure or minimalize several difficulties in creating comparable populations. I explore these tensions by highlighting three: the separation of difference from other aspects and categories of social experience, the reduction of difference through the use of one over several possible measures, and the enactment of difference as quantified knowledge loops back into society. I also draw on insights from feminist theory and science and technology studies to make sense of these difficulties. The continued development of this line of population science despite these tensions suggests that certain scientific priorities are made over others, including the privileging of standardization, simplicity, and reproducibility at the expense of full engagement with social heterogeneity. A collective social science that centers the role of values can help address this issue of similarity-difference as it pertains to questions of social justice by identifying and making explicit the various commitments made during processes of scientific evaluation.