The key question of the TissUUmaps project is the how the relationship between single cell gene expression and tissue morphology is involved in health and disease. Digital imaging of tissue samples (digital pathology) and genetic analysis by next generation sequencing are two rapidly emerging fields in pathology. Genetic analysis, and particularly transcriptomics, is rapidly evolving thanks to the impressive development of next generation sequencing technologies, enabling genome-wide single-cell analysis of DNA and RNA in thousands of cells at constantly decreasing costs. However, most of today’s available technologies result in a genetic analysis that is decoupled from the morphological and spatial information of the original tissue sample, while many important questions in tumor- and developmental biology require single cell spatial resolution to understand tissue heterogeneity. Within the TissUUmaps project we develop computational methods that bridge single cell gene expression with tissue morphology by combining spatially resolved high-throughput genomics analysis (in situ RNA sequencing) of tissue sections with digital image analysis of tissue morphology. Going beyond visual assessment of this rich digital data will be a fundamental component for the future development of histopathology, both as a diagnostic tool and as a research field.