The advent of genomic technologies has enabled for the first time the comprehensive cataloging of the mutations present in cancers, and is changing how these are treated. We have long known that cancers actually comprise a population of cells, and have suspected that these are not all alike. It is evident that distinct subpopulations within any given cancer have unique mutation patterns, which could until recently only be assessed as variants with sub clonal allele frequencies. Single cell genomics allows the molecular phenotyping and genotyping of individual cancer cells, revealing a remarkable diversity that forms the driver behind cancer evolution and drug resistance. In addition, as immunotherapies enter the clinic, the cellular basis of tumour responses—subpopulations of immune cells with cytotoxic function—can now be mapped quantitatively, promising more accurate methods of predicting responses as well as peptide vaccination strategies.