LGALS3, a member of the lectin family, has an important role in tumor progression through inhibition of apoptosis. LGALS3 shares several significant structural properties with BCL2. In this study, we examined the prognostic significance of LGALS3 and BCL2 in uniformly treated classical Hodgkin's lymphoma. Diagnostic tissues from 110 patients with uniformly treated classical Hodgkin's lymphoma were evaluated retrospectively by immunohistochemical analysis of LGALS3 and BCL2 expression. The median follow-up time was 6.2 years (range, 0.2-17.3 years). Twenty-seven patients (25%) expressed LGALS3 protein in Hodgkin/Reed-Sternberg cells, which was associated with poor overall survival and event-free survival (P=0.007 and P<0.001). Fifteen patients (14%) expressed BCL2 protein in Hodgkin/Reed-Sternberg cells, which was not associated with overall survival and event-free survival (P=0.928 and P=0.900).There was no correlation between LGALS3 and BCL2 expression (P=0.193). Multivariate analysis identified LGALS3 protein as an independent prognostic factor for event-free survival (P=0.007). Subgroup analysis according to the Ann Arbor stage of classical Hodgkin's lymphoma showed that LGALS3 protein expression had a prognostic value in limited-stage classical Hodgkin's lymphoma (P<0.001). The results of this study suggest that LGALS3 is an independent prognostic factor in classical Hodgkin's lymphoma, and may allow the identification of a subgroup of patients with limited-stage classical Hodgkin's lymphoma who require more intensive therapy.