Background The concepts of size and scale in nanotechnology are difficult for most beginning engineering students to grasp. Yet, guidance on the specific aspects of size and scale that should be taught and assessed is limited. Purpose This research sought to empirically develop a framework for size and scale conceptualization and provide a blueprint to guide curriculum development and assessment. Design/Methods Through an exploratory sequential mixed methods design, we qualitatively examined 30 teams of 119 first‐year engineering students' nanotechnology‐based projects to identify concepts beyond those in the literature to create a Size and Scale Framework (SSF). We then created a blueprint with associated learning objectives that can guide curriculum and assessment development. To demonstrate the utility of the SSF blueprint, an SSF‐based quiz was developed and studied using classical test theory with 378 first‐year engineering students. Results The findings categorized size and scale in terms of eight aspects: Definition, Qualitative Categorical, Qualitative Relational, Qualitative Proportional, Quantitative Absolute, Quantitative Categorical, Quantitative Relational, and Quantitative Proportional. The SSF can be applied as a blueprint for others to develop curriculum and assessment. The SSF‐based quiz demonstrated acceptable properties for use with first‐year engineering students. Conclusions Development of the SSF‐based quiz is an example of how the SSF can be applied to create a classroom quiz to assess students' size and scale knowledge in the context of nanotechnology.