The neutrophil/lymphocyte (N/L) ratio at diagnosis has been shown to be a prognostic factor for survival in solid tumors. The N/L ratio at diagnosis as a prognostic factor for non-Hodgkin lymphoma (NHL) has not been studied. Thus, we studied N/L ratio at diagnosis as a prognostic factor for patients with diffuse large B-cell lymphoma (DLBCL)treated with R-CHOP. From 2000 until 2007, 255 consecutive DLBCL patients, originally diagnosed, treated with R-CHOP, and followed at Mayo Clinic, Rochester, were included in this study. With a median follow-up of 4.0 years (range: 0.3-9.0 years), patients with an N/L ratio<3.5 at diagnosis experienced a superior overall survival (OS) and progression-free survival (PFS) compared with those patient with an N/L ratio ≥ 3.5 at diagnosis. The median OS was not reached versus 6.8 years, P < 0.0001; and the median PFS was not reached versus 3.3 years, P < 0.0001, respectively. Multivariate analysis showed N/L ratio to be an independent prognostic factor for OS and PFS. This study suggests that baseline N/L ratio at diagnosis is a simple, inexpensive,standardized prognostic factor to assess clinical outcomes in DLBCL patients treated with R-CHOP.