The introduction in pathology practice of a new biomarker that is contributing to define a disease requires a series of investigations. Now that new biomarkers are being discovered continuously it is important to learn from successful examples of markers that are presently widely used. In this historical account the steps are described that have led to the use of immunohistochemical staining of tissue samples with an antibody against cyclinD1 to diagnose mantle cell lymphoma. Furthermore, a short outlook is given on the introduction of proteomics as a tool in the diagnosis of lymphoma and the potential route to be taken for introducing this technology into clinical practice.