Introduction: Ovarian cancer is the most lethal gynecological malignancy. Mechanisms involved in the progression of primary high-grade serous carcinoma (HGSC) into metastatic carcinoma are not understood. Nicotinamide N-methyltransferase (NNMT) is overexpressed in cancer, and its overexpression leads to epigenetic changes through hypomethylation of histones. It plays a role in epithelial–mesenchymal transition and sustenance of cancer stem cells. NNMT expression in primary and metastases of ovarian carcinoma and its relationship with survival have not been studied before. Materials and Methods: We compared the expression of NNMT between primary and matched synchronous metastatic carcinoma of patients, diagnosed with HGSC. Benign ovarian and omental tissues were used as controls. The relationships between NNMT expression and relapse-free and disease-specific survival were analyzed. Results: NNMT expression in metastases was significantly higher than matched primary carcinoma. NNMT was overexpressed in the stroma of primary and metastatic tumors. Increased NNMT expression was associated with decreased relapse-free and disease-specific survival. Conclusion: This study detected a higher expression of NNMT in metastases of HGSC compared to matched primary and associated increased metastatic NNMT expression with decreased survival. Upregulation of NNMT in tumor stroma suggests it plays a role in desmoplasia. Targeting of NNMT and desmoplasia may play a critical role in the treatment of HGSC.