Breast cancer is a highly heterogeneous disease, and intratumoral heterogeneity is not limited to genomic heterogeneity. Using lentiviral-based cellular barcoding technologies including genetic and optical barcoding, we are currently investigating the fate of human breast cancer clones in multiple tumour microenvironments. These technologies allow us to study the spatio-temporal evolution of the clones in specific tumour microenvironments, and to link this information to their molecular profile and fate in other organs. In combination with other technologies such as high-resolution imaging, single-cell sequencing, and other -omics analysis, cellular tracking facilitates the analysis of subclonal heterogeneity in complex mechanisms associated with disease progression.