Mantle cell lymphoma (MCL), a subtype of B-cell non-Hodgkin lymphoma, is usually incurable with current therapeutic approaches and the clinical course displays considerable variability. Objective assessment of the efficacy of new and more tailored treatment strategies requires deeper molecular insights into the disease and more individual risk assessment. The molecular feature of tumor cell proliferation as measured by Ki-67 immunohistochemistry or, more precisely, by microarray-based gene-expression profiling, has been shown to be of strong predictive value in MCL. The recently proposed quantitative reverse transcription-PCR based five-gene model survival predictor is applicable to fresh-frozen and routinely obtained formalin-fixed and paraffin-embedded tumor tissues, and provides the potential to investigate its prognostic value in prospective clinical trials of MCL patients.