<p>Model organisms (MOs) are indispensable in modern biological and biomedical research, yet frameworks for their evaluation remain underdeveloped. In particular, no consensus exists on how, and to what extent, findings from one species can be generalized to others, including humans. We address this gap by introducing a comprehensive, multi-criteria framework that integrates both internal and external validity. We propose to assess internal validity by examining the reliability of experimental measurements and the inferences that translate those data into biological phenomena. External validity, or generalizability, is guided by four distinct types of similarity — material, functional, manipulation-induced, and phenomenological — each situated at explicit biological levels (molecular, cellular, physiological, etc.) and qualified by their evidential strength. We unite these elements under the metaphor of a “validity ladder”: each well-supported similarity adds a rung linking the model to its target, and the ladder remains dynamic — new data may reinforce existing rungs, add stronger ones, or reveal weak links. The overall robustness of the scale also depends on how rungs, or similarities, across biological levels interconnect (what we call “cross-links”). Importantly, the specific research objective guides the evaluation process, assigning greater or lesser weight to each rung. By formalizing this procedure, our framework not only enriches the philosophical understanding of MOs as representational and interventional tools but also provides researchers with operational criteria for designing, interpreting, and refining model-based studies.</p>