The introduction of light microscopy in 1872 by Ernst Abbe and Carl Zeiss was one of the first revolutionary steps in the diagnosis of human diseases. It was possible to determine associated structural defects by morphological analysis of tissues and single cells, resulting in the development of major classifications and subgroup definitions. These have been revised many times during the last 130 years and continue to have an huge impact on modern diagnostics. For decades during the last century, light microscopy was one of the most important methods available for the clinical diagnosis of tumors and for describing morphological changes associated with widespread disorders, such as diabetes and heart disease.

From chromosomal analysis in the 1960s, molecular biological methods, polymerase chain reaction, and immunological methods, such as immunofluorescence, which enables us to define the surface marker profile of single cells, have been introduced into disease diagnosis. Examples are: the discovery of the Philadelphia-Chromosome t(9;22) as the main feature of chronic myeloid leukemia (CML); the association of HLA-DR subtypes with specific diseases (e.g., HLA B27 in patients with Bechterew's disease); and mutations of the APC gene in patients with colon cancer. By using such single genetic markers, the risk stratification of these diseases has been improved, resulting in more specific treatment with better clinical long-term outcomes. In particular, for CML, it was possible to use the well-characterized molecular defect to design the first target-specific drug (STI571, Imatinib™), dramatically improving the treatment options for patients with Ph + leukemias.