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A common feature of these diseases is the presentation of multiple primary tumours, or multifocal disease representing independent tumour clones that have arisen from the same initiating genetic lesion, but have undergone independent clonal evolution. Such tumours provide an opportunity to discover common cooperative changes required for tumourigenesis, while controlling for the genetic background of the individual. We performed genomic analysis of synchronous and metachronous tumours from five patients bearing germline mutations in the genes <jats:italic><jats:styled-content style=\"fixed-case\">SDHB<\/jats:styled-content><\/jats:italic>, <jats:italic><jats:styled-content style=\"fixed-case\">RET<\/jats:styled-content><\/jats:italic>, and <jats:italic><jats:styled-content style=\"fixed-case\">MAX<\/jats:styled-content><\/jats:italic>. Using whole exome sequencing and high\u2010density single\u2010nucleotide polymorphism arrays, we analysed two to four primary tumours from each patient. We also applied multi\u2010region sampling, to assess intratumoural heterogeneity and clonal evolution, in two cases involving paraganglioma and medullary thyroid cancer, respectively. Heterogeneous patterns of genomic change existed between synchronous or metachronous tumours, with evidence of branching evolution. We observed striking examples of evolutionary convergence involving the same rare somatic copy\u2010number events in synchronous primary phaeochromocytoma\/paraganglioma. Convergent events also occurred during clonal evolution of metastatic medullary thyroid cancer. These observations suggest that genetic or epigenetic changes acquired early within precursor cells, or pre\u2010existing within the genetic background of the individual, create contingencies that determine the evolutionary trajectory of the tumour. Copyright \u00a9 2017 Pathological Society of Great Britain and Ireland. 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