As patients with multiple myeloma (MM) have a variable clinical course, predictive markers would help determine the appropriate treatment strategy. Clinical staging is commonly used to predict outcome, but tumour marker expression and the underlying genetic changes are increasingly used to assess the biological aggressiveness of the disease. Recent studies have demonstrated the utility of immunohistochemistry in detecting prognostic markers, including fibroblast growth factor receptor 3, cyclin D1, c-maf and p53, which have been associated with various genetic aberrations, including t(4;14), t(11;14), t(14;16) and del(17p). While t(4;14), t(14;16) and del (17p) have been documented to confer a poor prognosis, t(11;14) appears to be a neutral or even favourable factor in some studies. CD56, CD33, CD20 and CXCR4 are promising surface markers due to their roles in MM progression, but further studies of larger cohorts are necessary to assess their prognostic relevance. In this review, the biological function and clinical relevance of the main prognostic markers in MM is discussed, and also the role of immunohistochemistry in the stratification of patients into appropriate risk categories.