Collapsing glomerulopathy frequently shows focal lesions on biopsy, creating challenges with transcriptomic investigations because of inadequate tissue sample. This challenge is overcome with spatial transcriptomics, technology linking transcriptomic data to histology. Applying this technology to investigate patients with collapsing glomerulopathy related to HIV infection or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Smith et al. provide provocative evidence that collapsing glomerulopathy may have different molecular signatures despite the similar morphologic appearance.