The complexity of the metastatic process has made it difficult to gain a full understanding of the origins of this most lethal aspect of cancer. Many factors probably have an important role, including somatic mutation, epigenetic modulations, interactions with normal stroma, and environmental stimuli. Additionally, recent evidence implies a significant role for germline polymorphisms in cancer progression. The existence of inherited metastasis risk factors (or prospective metastatic biomarkers) has potentially significant implications for our models of metastasis, clinical prognosis and the development of tailored treatment. Further investigations into the inherited components of metastasis might help resolve many of the questions that remain about tumour progression.