Serum sickness (SS) and anaphylaxis are well-documented complications of rituximab (RTX) infusions. While the first presents usually as a triad of fever, rash, and arthralgias occurring seven to 14 days after infusion, the second presents as a sudden onset of hemodynamic instability, bronchospasm, and a pruritic erythematous rash, occurring within the first few hours after infusion. We present here a case of serum sickness associated with anaphylaxis five days after the first infusion of a second course of RTX. Only eight cases of rituximab-induced serum sickness (RISS) associated with hemodynamic instability have been reported. We describe the first case of proven anaphylaxis with an elevated tryptase serum level occurring in conjunction with RISS, six days after a third RTX infusion.