Tumor lysis syndrome (TLS) is a life-threatening condition caused by the rapid destruction of malignant cells, leading to imbalances in electrolytes and posing risks such as acute kidney injury, arrhythmia, and seizures. This retrospective study aimed to evaluate the incidence of TLS in a cohort of 94 patients with advanced-stage aggressive B-cell malignancies treated with fractionated rituximab, along with usual TLS preemptive measures such as hyperhydration and urate-lowering treatments. The study found that TLS occurred in seven patients, with one case classified as clinical TLS (cTLS) and six as laboratory TLS (lTLS). The incidence of TLS was higher in patients with Burkitt lymphoma compared to diffuse large B-cell lymphoma. TLS occurrence did not significantly influence survival outcomes in this cohort. Comparison with other datasets showed similar TLS rates in patients with high-grade B-cell lymphoma. These findings contribute to the understanding of TLS in B-cell malignancies, highlighting the potential of fractionated rituximab as a debulking approach to manage TLS risk that warrants further investigation in prospective trials.