The greater omentum represents a specific adipose tissue resected with gastric surgery for cancer. Diffuse gastric adenocarcinoma (diffuse-GC) is of major relevance among gastric cancers due to its unknown origin, aggressiveness, and metastasis in the peritoneal cavity. We postulated that persistent organic pollutants (POPs) could be detected in the greater omentum. Great omentum from patients with (i) diffuse-GC, or (ii) with other peritoneal metastatic cancer, and (iii) control group without cancer disease were analyzed for the distribution of a large panel of 96 POPs. POPs include polychlorinated dioxins/furans (PCDD/Fs), polychlorobiphenyls (PCBs), polybrominated diphenyl ethers (PBDE), polybrominated biphenyls (PBB), hexabromocyclododecanes, organochlorine pesticides, and polycyclic aromatic hydrocarbons (PAHs). The widespread presence of a substantial list of POPs (PCDDs/Fs, PCBs, and brominated flame retardants) was found in the omentum from patients with aggressive diffuse-GC, with minor presence of some organochlorine pesticides and PAHs at the low analyzed levels. Some chemicals appeared in larger concentrations in diffuse-GC or other cancer groups, including some PCDDs, PCB105, 123, 138, PBDE209, and PBB153. Overall, the present pilot study provides novel information regarding POPs levels in the omental fat, which is an understudied fat depot in terms of POPs load, and diffuse-GC association.