Glioblastomas (GBMs) diffusely infiltrate the brain, making complete removal by surgical resection impossible. The mixture of neoplastic and non-neoplastic cells that remain after surgery form the biological context for adjuvant therapeutic intervention and recurrence. We performed RNA-Seq and histological analysis on radiographically guided biopsies taken from different regions of GBM and showed that the tissue contained within the contrast-enhancing (CE) core of tumors have different cellular and molecular compositions compared to tissue from the non-enhancing (NE) margins of tumors. Comparisons with the TCGA dataset showed that the samples from CE regions resembled the Proneural, Classical, or Mesenchymal subtypes of GBM, while the samples from the NE regions predominantly resembled the Neural subtype. Computational deconvolution of the RNA-seq data revealed that contributions from non-neoplastic brain cells significantly influence the expression pattern in the NE samples. Gene ontology showed that the cell type-specific expression patterns were functionally distinct and highly enriched in genes associated with the corresponding cell phenotypes. Comparing the RNA-Seq data from the GBM samples to that of normal brain revealed that the differentially expressed genes are distributed across multiple cell types. Notably, the patterns of cell type-specific alterations varied between the different GBM subtypes; the NE regions of Proneural tumors were enriched in oligodendrocyte progenitor genes while the NE regions of Mesenchymal GBM were enriched in astrocytic and microglial genes. These subtype-specific patterns in the molecular and cellular composition of the infiltrative margins of GBM make it possible to infer key characteristics of the tissue left behind after surgery.