Multiple myeloma (MM) is a B-cell malignancy characterised by the accumulation of clonal plasma cells (PC) in the bone marrow (BM). The molecular bases for this incurable disease have been widely investigated in the last years, and the development of modern genomic technologies has contributed to the understanding of the pathogenesis of MM. The molecular mechanisms that explain the cellular origin of myeloma cells, the cytogenetic abnormalities and their clinical implications, and the biological information provided by gene expression profiling analysis are reviewed in this paper. In addition, a molecular classification of MM in seven groups based on the relationship between gene expression profiling, chromosomal translocations and prognostic outcome is also presented. And finally, the recent hypothesis of a potential unifying event in the pathogenesis of MM, supported by cyclin D deregulation in virtually all MM tumours, will be summarised.