Background: Respiratory epithelial adenomatoid hamartoma (REAH) is a proliferative lesion of the nasal mucosa with unknown aetiology. Omics approaches revealed allelic changes, altered protein expression and infiltration of a heterogeneous immune cell population. Spatial profiling techniques offer new opportunities to study immune cell distribution and cell-cell communication in REAH that may assist the understanding of its pathogenesis. This pilot study investigated the feasibility of spatial profiling to better understand the biological processes driving the proliferative aspect of REAH. Methods: Formalin-fixed paraffin embedded slides of sinonasal biopsies from patients with REAH and patients with inflammatory polyps were collected. The slides were stained and analysed on the NanoString GeoMx™ DSP platform using the Cancer Transcriptome Atlas for interrogation of tumour and immune cell compartments. Sequencing was completed on a NovaSeq 2000. Data was normalised by TMM with edgeR (v3.36) and differential expression calculated with limma (v3.50.3). Significance was considered with adjusted and unadjusted p-values. Functional enrichment was calculated using a rank-based gene set enrichment approach (FGSEA) with the FGSEA R package (V1.20). Results: Age and sex matched REAH, nasal polyp and healthy samples were analysed. Changes in gene expression confirmed differences between REAH and polyps in immune cells and inflammatory programs. Changes in key inflammatory signalling pathways included canonical and non-canonical cancer, immune and evasion pathways. Within the immune cell compartment, transcriptomic deconvolution identified 8 different immune cell types. Conclusion: This the first study applying spatial profiling to examine REAH to understand its disease mechanisms. Our study confirmed dysregulation of several canonical cancer pathways and novel inflammatory pathways in REAH and the utility of spatial technologies to improving our understanding of this disease.