Background Recent reports suggest genetic polymorphisms influence susceptibility to rituximab induced late-onset neutropenia (LON), which in turn may be a predictor of good outcome in B-cell lymphoma. Aims We report the largest study to date assessing FCGR3A-V158F polymorphisms in Diffuse Large B-cell Lymphoma (DLBCL) treated with CHOP-R. The influence of C1qA-A276G polymorphisms in DLBCL, and the impact of both polymorphisms on susceptibility to LON and outcome were also examined. Methods 115 DLBCL patients treated with CHOP-R were compared with 105 healthy Caucasian controls with regards to FCGR3A-V158F and C1qA-A276G polymorphisms . LON incidence and event free and overall survival (EFS and OS) were analysed for linkage to either polymorphism. Results The FCGR3A-V158F but not the C1qA-A276G polymorphism influenced the risk of developing LON. 50% of FCGR3A-158V/V patients experienced LON. In contrast, only 7% V/F and 2% F/F experienced LON. The FCGR3A-158V/V genotype was associated with LON compared to V/F (p=0.028) and F/F genotypes (p=0.005). Although no patients with either LON or FCGR3A-158V homozygosity relapsed compared to 33% FCGR3A-158F/F and 21% non-LON, this did not translate into improved EFS or OS. Conclusions Polymorphic analysis may be a predictive tool to identify those at high-risk of LON. Prospective studies are required to definitively establish if LON or FCGR3A-158V/V genotype influences outcome.