Dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin-related protein (DC-SIGNR), a type II integral membrane protein and a member of the C-type lectins, has been reported to bind various strains of HIV-1, HIV-2, and simian immunodeficiency virus. Serum DC-SIGNR is not currently available for the detection of non-Hodgkin lymphoma (NHL). Using an enzyme-linked immunosorbent assay (ELISA), we assessed the serum levels of DC-SIGNR in 70 cancer patients and 100 healthy controls. Additionally, using immunohistochemistry, we determined the expression of DC-SIGNR in the lymph nodes. Using the ELISA, low serum levels of DC-SIGNR were detected in the patients (median, 4.513 ng·L(-1); range, 1.066-9.232 ng·L(-1); p = 0.0003). Serum concentrations of DC-SIGNR correlated significantly with age (p = 0.0077) and lactic acid dehydrogenase (p = 0.0046) and β2-microglobulin (p = 0.0491) levels. However, we found no statistically significant correlation between serum DC-SIGNR levels and clinical data such as sex, Ann Arbor stage, B symptoms, and histologic subtypes. Moreover, NHL patients with a lower level of serum DC-SIGNR expression in lymphatic endothelial cells also showed negative immunostaining levels. These results suggest that DC-SIGNR is a biological molecule that may be potentially useful in NHL clinical settings.