Multicellular organisms, organs and tissues are composed of many different cell types characterized by extensive interactions. A clear understanding of the mutual dependencies of different cells is essential to assign each cell its role in physiology and pathophysiology. With few exceptions, normal cells operate on the basis of the same genome. However, cancer cells show a high degree of genetic variation, each being genetically unique. For this reason, comprehensive analysis of the genetic composition of individual cancer cells is crucial for a deep understanding of development and progression of systemic cancer. Furthermore, genetic characteristics of cancer cells change during disease progression, requiring repeated genome analyses, in particular after primary tumor resection, but before the occurrence of distant metastases. During this phase of disease progression only very few cancer cells (circulating tumor cells in the blood or disseminated cancer cells that invaded other organs such as lymph nodes, bone marrow, or cerebrospinal fluid) can be found and isolated. These rare cells offer the possibility to identify therapeutically relevant mutations and to select tailored therapies for patients, thereby preventing systemic progression of the disease at an early stage. Fraunhofer ITEM in Regensburg develops advanced next-generation sequencing technologies including matched quality control assays to reliably analyze the comprehensive genetic information of a single cell. This provides new opportunities not only for molecular diagnostics in precision oncology, but also for the investigation of pathophysiological processes with rare driver cells.