Rituximab or Rituxan is a common drug used in the treatment of lymphomas. It is almost always used in conjunction with other chemotherapy regimens. Mechanism of action involves killing of the CD 20+ cells. Rituximab is implicated in precipitating tumor lysis syndrome (TLS) in patients with diffused large B cell lymphoma (DLBCL). The precise pathophysiological mechanism is not well known. Here, we present a case where the patient only received Rituxan for her newly diagnosed B-cell lymphoma which triggered a tumor lysis cascade. This in turn resulted in multiple electrolyte disturbances, multi-organ failure, and mortality. This report discusses the case presentation in addition to the different types of TLS and how this knowledge can be applied in the clinical setting for the future.