Multiple reports highlight the increasingly quantitative nature of biological research and the need to innovate means to ensure that students acquire quantitative skills. We present a tool to support such innovation. The Biological Science Quantitative Reasoning Exam (BioSQuaRE) is an assessment instrument designed to measure the quantitative skills of undergraduate students within a biological context. The instrument was developed by an interdisciplinary team of educators and aligns with skills included in national reports such as BIO2010, Scientific Foundations for Future Physicians, and Vision and Change Undergraduate biology educators also confirmed the importance of items included in the instrument. The current version of the BioSQuaRE was developed through an iterative process using data from students at 12 postsecondary institutions. A psychometric analysis of these data provides multiple lines of evidence for the validity of inferences made using the instrument. Our results suggest that the BioSQuaRE will prove useful to faculty and departments interested in helping students acquire the quantitative competencies they need to successfully pursue biology, and useful to biology students by communicating the importance of quantitative skills. We invite educators to use the BioSQuaRE at their own institutions.