Molecular genetic analysis adds important information for lymphoma biology and classification, but the latter is challenged by recent improvement of combined chemo-immunotherapy. In aggressive lymphoma, molecular profiling identifies risk groups with certain genetic background but still the International Prognostic Index (IPI) remains the most important clinically applicable predictor of outcome. In follicular lymphoma (FL), the importance of the meshwork of bystander cells becomes increasingly evident. As combined immuno-chemotherapy improved the prognosis of the patients, several clinical trials indicated that the FLIPI still efficiently discriminates patients at risk for transformation and relapse, although several mechanisms of transformation seem to exist. In mantle cell lymphoma it has been proven that pathogenesis and prognosis mainly depend on deregulation of the cell cycle. A reliable clinical risk score could be established.