Papillary thyroid microcarcinoma accounts for a large proportion of papillary thyroid carcinoma, especially among new cases. Many PTMC patients have regional lymph node metastasis, with some experiencing recurrence and even death. However, the risk factors and mechanism by which PTMC relates to these factors are unknown. In this study, differentially expressed genes were identified with microarray from The Cancer Genome Atlas, followed by analysis using the Kyoto Encyclopedia of Genes and Genomes. Immunohistochemistry, immunofluorescence, western blot and Oil Red O staining were carried out to evaluate expression levels and functional alterations. Mesenteric Estrogen Dependent Adipogenesis expression was observed in almost all cases of papillary thyroid microcarcinomas, and the location of expression was associated with histological subtype. High expression was correlated with metastasis and poor disease-free survival. Furthermore, the enrichment analysis indicated that Mesenteric Estrogen Dependent Adipogenesis expression may be associated with metabolic reprogramming to influence metastasis and prognosis. These findings contribute to a better understanding of how Mesenteric Estrogen Dependent Adipogenesis affects metastasis and the prognosis of papillary thyroid microcarcinoma patients and suggest that Mesenteric Estrogen Dependent Adipogenesis expression may be a novel prognostic marker in these patients.