Across large chemical databases including Enamine 350/3, Mcule, and ChEMBL, consistent trends emerge regarding which skeletal editing transformations stand to most significantly increase commercially accessible chemical space for heteroaromatic compounds. Despite variations in database size and composition, virtual ring contractions of heteroaromatics often give fewer characterized or commercially available products as compared to the range of products accessible using ring expansion or atom transmutation skeletal editing transformations. This quantitative analysis highlights the need for new synthetic methodologies that can efficiently modify heteroaromatics such as pyridines, pyrimidines, and pyrroles through precise single-atom changes in the cores of these molecules. Transformations of this type would significantly expand the structural diversity of the currently accessible chemical space for pharmaceutically relevant compounds and other applications. According to this analysis, skeletal edits of pyrimidines, thiazoles, and pyrroles would most significantly enhance access to novel chemical space. Additionally, pyrroles emerged as a valuable target product for skeletal editing reactions of several heteroaromatics.