Vertical sleeve gastrectomy (VSG) is a surgical weight loss procedure that resects 80% of the stomach, creating a tube linking the esophagus to the duodenum. Because of the efficacy and relative simplicity of VSG, it is preferred in the United States, with VSG currently at >61% of bariatric surgeries performed. Surprisingly, there has never been a complete molecular characterization of the human stomach greater curvature's fundus and corpus. Here we compare and contrast the molecular makeup of these regions. We performed a prospective cohort study to obtain gastric tissue samples from patients undergoing elective VSG. Paired fundus and corpus samples were obtained. Whole genome transcriptome analysis was performed by RNA sequencing (N = 10), with key findings validated by qPCR (N = 24). Participants were primarily female (95.8%) and White (79.15%). Mean body mass index, body weight, and age were 46.1 kg/m2, 121.6 kg, and 43.29 yr, respectively. Overall, 432 gene transcripts were significantly different between the fundus and the corpus (P < 0.05). A significant correlation was found between the RNA sequencing dataset and qPCR validation, demonstrating robust gene expression differences between the fundus and the corpus. Significant genes included progastricsin, acidic chitinase, and gastokine 1 and 2 in both the fundus and the corpus. Of the very highly expressed genes in both regions, 87% were present in both the stomach's fundus and corpus, indicating substantial overlap. Despite significant overlap in the greater curvature gene signature, regional differences exist within the fundus and the corpus. Given that the mechanism of VSG is partly unresolved, the potential that the resected tissue may express genes that influence long-term body weight regulation is unknown and could influence VSG outcomes.