The tumor microenvironment (TME) comprises a mixture of cell types, including tumor cells, cancer subclones, metaplasia, dysplasia, desmoplasia, reactive fibroblasts, and a complex immune response of macrophages and lymphocyte subclasses. Measuring the molecular status of each cellular component within the TME is important to understanding tumor initiation and progression as well as in determining the interplay between cancer and normal host cells. However, today most molecular analyses of tumors are performed on heterogeneous bulk samples or on crudely macrodissected cell populations, typically mixing together multiple different cells types and generating only limited spatial context. Thus, essential positional information on the TME is not available. The proposal describes a new DNA sequencing and genomic analysis technology for histological slides called spatial micropurification, which can be developed into a commercial device that will permit localized, cell-type specific interrogation of the tumor micro-environment (TME). Development and deployment of this novel technology for spatial molecular profiling of tumors will provide a deeper understanding of the relationship between cell genotype and morphology, providing valuable information toward development of new diagnostic, prognostic, or therapeutic interventions for patients with cancer.