Many students in upper-division physics courses struggle with the mathematically sophisticated tools and techniques that are required for advanced physics content. We have developed an analytical framework to assist instructors and researchers in characterizing students' difficulties with specific mathematical tools when solving the long and complex problems that are characteristic of upper division. In this paper, we present this framework, including its motivation and development. We also describe an application of the framework to investigations of student difficulties with direct integration in electricity and magnetism (i.e., Coulomb's law) and approximation methods in classical mechanics (i.e., Taylor series). These investigations provide examples of the types of difficulties encountered by advanced physics students, as well as the utility of the framework for both researchers and instructors.