The chimeric monoclonal IgG1 antibody directed to CD20 Rituximab is used to treat various haematological malignancies and auto-immune diseases. Serum sickness is a type III hypersensitivity reaction leading to the formation and tissue deposition of immune antibody-antigen complexes. It has been described as a very rare complication of Rituximab treatment, mainly seen in patients treated for auto-immune diseases. We report the case of a patient with Waldenstrom’s macroglobulinaemia whose Rituximab treatment was complicated by documented immune complex deposition or serum sickness. We successfully applied a Rituximab desensitisation protocol, which allowed us to complete treatment.