The stromal component within solid tumors has been reported to be associated with poor prognosis or contrastingly in a minority of cancers with improved survival. We report the estimation of the percentage of stroma (POS) using digital pathology in a large population-ascertained cohort of primary melanomas. Consent was obtained from participants in the Leeds Melanoma Cohort Study to access and sample tumor FFPE blocks. H&E-stained slides were digitally scanned and blocks were sampled for gene expression studies using a tissue microarray needle; this yielded a core of tissue from which RNA was extracted and assayed using Illumina WGDASL. The cored region of the block was mapped onto the digital pathology image and POS was recorded. ESTIMATE was used to impute the extent of stroma from the expression data and this was compared with the histologically-generated measure. Metacore was used to assess the gene expression biologic pathways associated with the POS. Immunohistochemistry (IHC) was performed on a subset of samples to assess the expression of proteins associated with POS.