Rituximab is a commonly utilized treatment agent for B-cell lymphoma. Late onset neutropenia (LON) has been identified as a complication associated with rituximab, primarily in conjunction with hematopoietic stem cell transplantation (HSCT). Scant data exists regarding rituximab-related LON outside the spectrum of HSCT, including newly-diagnosed lymphoma. We examined a large cohort of newly-diagnosed B-cell lymphoma patients treated with rituximab-based therapy. We identified patients with LON and analyzed the characteristics and outcomes. Furthermore, we utilized multiplex PCR for the detection of the FcgRIIIa 158 V/F polymorphism and correlated this with LON. Eighty consecutive B-cell lymphoma patients were examined. Nine of 80 (11.3%) patients developed LON. The clinical course of LON was generally self-limiting without adverse events. The onset of LON occurred at a mean of 66 days after the last course of treatment, while the mean duration of LON was 97 days. Moreover, the V/V and V/F polymorphisms were significantly associated with the occurrence of LON (P 5 0.046) yielding an odds ratio for the development of LON of1.47 (95% CI 1.21-1.78). We identified an incidence of LON following frontline rituximab-based treatment of 11.3%. The FcgRIIIa polymorphism was highly associated with development of LON.