Research into the three-dimensional (3D) organization of the cancer cell genome started over 100 years ago. We follow an exciting avenue of research in this field, from Hansemann's early observations of aberrant mitoses and nuclei in cancer cells in the late 19th century to Boveri's theory of the cancer cell in the early 20th century, to current views of nuclear organization and its changes in cancer. Molecular and imaging methods go hand in hand with providing us with a better understanding of the spatial nature of the cancer cell genome. This has led to the concept that the structural order of the nucleus can be used as cancer cell biomarker.