BACKGROUND: The objective of this study was to compare the clinical features and prognosis of patients with diffuse large B-cell lymphoma (DLBCL) of Waldeyer ring (WR-DLBCL) and patients with lymph node DLBCL (N-DLBCL). METHODS: One hundred eighty-one patients with WR-DLBCL and N-DLBCL were reviewed. There were 57 patients with stage I disease, 83 patients with stage II disease, 26 patients with stage III disease, and 15 patients with stage IV disease. Among them, 101 patients had primary N-DLBCL, and 80 patients had primary WR-DLBCL. RESULTS: Patients with WR-DLBCL and N-DLBCL usually presented at an older age and had localized disease, a low frequency of B symptoms, a good performance status, and a low-risk International Prognostic Index (IPI) score. Compared with patients who had N-DLBCL, patients who had WR-DLBCL presented with more stage II disease and lower tumor burdens. The overall response rate after treatment was similar in both groups. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 76% and 61% in patients with WR-DLBCL, respectively, and 56% and 50% in patients with N-DLBCL, respectively (P = .119 for OS; P = .052 for PFS). IPI scores and elevated β2-microglobulin and LDH levels were associated with a poor prognosis for patients who had WR-DLBCL; whereas bulky tumor, elevated β2-microglobulin levels, and IPI scores were associated with poor OS for patients who had N-DLBCL. CONCLUSIONS: The current results supported the continued inclusion of WR-DLBCL as a lymph node group in the staging of DLBCL. Patients with WR-DLBCL had clinical features and prognosis similar to those of patients with N-DLBCL. © 2009 American Cancer Society.