Scale, proportion, and quantity constitute a “crosscutting concept” in science education – a concept that pervades science and can help students connect their knowledge across topics and disciplines. An understanding of wide ranges of size is a prerequisite for the learning of scale. Students must have a good understanding of size and scale if they are to leverage them to connect their science understanding. In this study, we examine two qualitatively different types of knowledge that may underlie the understanding of size and scale: the evolutionarily-based approximate number sense, and the culturally-based understanding of measurement units. We explore how closely these two types of knowledge are related to size and scale knowledge useful for secondary science classrooms. This study has implications for instruction: evolutionarily-based abilities are biologically primary, are acquired universally, and are motivating, whereas culturally-based abilities are biologically secondary, and depend on instruction, practice, and external motivation. Different educational approaches might be better suited to biologically primary and secondary abilities. The results of an empirical study with 36 seventh grade students are reported.