With the advent of atomistic modeling and high-performance computing, the search for crystalline compounds that are distinct from previously explored systems is an ever-growing problem. The multitude of different crystal representations exacerbates the issue, obfuscating structural similarity. To explore novel regions of materials space, tools are required to i) accurately characterize a crystal’s structure, ii) automatically generate coordinate models of new compounds, and iii) ensure uniqueness within datasets. Herein, three modules developed in the Automatic FLOW (AFLOW) framework are briefly highlighted that satisfy these needs. First, AFLOW-SYM – a symmetry calculator – is presented, featuring adaptive algorithms to identify the complete symmetry profile of a crystal consistent with experiments. Next, the AFLOW Prototype Encyclopedia is discussed: an extensive catalog of structure-types coupled with software to generate any possible crystallographic compound. Finally, a module – AFLOW-XtalFinder – is described, which identifies and classifies a material’s prototype and determines structural uniqueness within user-defined and established repositories. Together, these tools robustly characterize a crystal’s symmetry and prototype designation, reveal similarity between structures, and create hypothetical systems for materials discovery. They also enable the identification of solid solution high-entropy ceramics for extreme environments and fuel the continued growth of the AFLOW.org repository, currently comprised of 3.5+ million material entries.