Bortezomib (VELCADE) is a proteasome inhibitor, which has been recently used for the treatment of relapsed/refractory multiple myeloma (MM) with encouraging results. Tumour lysis syndrome (TLS) has been described during chemotherapy for many haematological malignancies, such as acute lymphoblastic leukaemia and high-grade lymphomas. TLS is very rare in MM with ten reported cases, including approximately 1% of patients receiving high-dose chemotherapy with stem cell support (ASCT). We report here a patient with refractory MM and deletion 13q, who had received more than four lines of previous treatment, including two ASCT, and had relapsed. The patient received bortezomib, as a single agent, at a dose of 1.3 mg/m(2) twice per week for 2 weeks, in a 3-week cycle, and developed TLS after the second dose of cycle one. Bortezomib therapy, due to the rapidity of its action, may result in TLS in myeloma patients who have rapidly proliferative disease with a high tumour burden. Therefore, TLS should be looked for during the first cycle of bortezomib treatment and suitable precautions should be considered.