This study aimed to conduct an in-depth examination of gene expression and microenvironmental profiles of gastric neuroendocrine carcinoma (NEC) and mixed adeno-neuroendocrine carcinoma (MANEC). Tissue microarrays from 55 patients with gastric MANEC (N=32) or NEC (N=23) were analysed using digital spatial profiling (GeoMx® DSP). Representative regions of interest (ROIs) were selected from the adenocarcinoma portion (ADC-MANEC) and neuroendocrine carcinoma portion (NEC-MANEC) of the MANEC cores, and pure NEC (pNEC) cores. All ROIs were separated into epithelial components and stromal components by the masking procedure in GeoMx® platform, followed by transcriptome analysis. Comparison of gene expression between ADC-MANEC and NEC-MANEC/pNEC identified several differentially expressed genes in the epithelial (including PEG10, MAP1B, STMN3, and AKT3) and stromal (FN1, COL1A1, SPARC, and BGN) components. Gene set enrichment analysis revealed that pathways related to the E2F target and G2M checkpoint were more enriched in NEC-MANEC and pNEC than in ADC-MANEC. Deconvolution analysis showed that the microenvironmental profile varied according to histologic differentiation. In ADC-MANEC, intraepithelial infiltrating immune cells were relatively more numerous, while fibroblasts in the stroma were more abundant in NEC-MANEC and pNEC. This study confirmed the distinct expression profile of each histological component of MANEC according to its tumour versus stromal compartment using the DSP platform. Although each component of MANEC shares the same genetic origin, distinctive phenotypes should not be overlooked when managing patients with MANEC. This study provides a useful validation dataset for future studies.