Abstract: Methods for determining a prognosis in multiple myeloma are disclosed, and in particular to methods that are capable of identifying patients with a poor prognosis and/or for determining the likelihood of a patient responding to a particular treatment. The methods identify myeloma samples having homozygous deletions in cell death genes, with dysregulated expression of 97 cell death genes forming a cell death expression signature, which is associated with poor prognosis in multiple myeloma. In a preferred aspect, three gene pairs, were found to provide a prognostic a “six gene signature” based on BUB1B and HDAC3; CDC2 and FIS1; and RAD21 and ITM2B (high expressors and low expressors respectively).