This chapter outlines the contribution of inherited genetic variation to cancer susceptibility and of acquired somatic mutations to cancer growth. The chapter deals with all forms of cancer susceptibility from rare, high-penetrance Mendelian syndromes to common alleles with small effects with importance for population risk. The section on somatic cancer genetics deals with underlying processes, such as genomic instability, and the types of functional change that result in the growth of both benign and malignant tumors. Genetic and epigenetic changes in cancers, from chromosomal scale to small mutations, are discussed. Overall, rather than performing an exhaustive survey in this large field, the chapter outlines the principles of cancer genetics using examples from both common and rare tumor types.