This chapter aims to review some of the critical landmark developments in the field of cancer genetics which have allowed such amazing progress in our understanding of cancer development in such a relatively short time. The ability to map unique sequences to particular regions of chromosomes was a more controversial issue. The role of oncogenes as active instigators of malignant transformation was established by a number of lines of evidence. The ease of manipulation of bacterial artificial chromosomes made these clones the clones of choice in systematic high throughput sequencing efforts. The ultimate proof was to sequence the gene which was relatively straightforward if RNA was available and if the mutation was such that a stable RNA was made. The other approach was to sequence the individual exons of a gene directly from the DNA template after polymerase chain reaction amplification.