Increasing evidence indicates that ion channels are involved in the pathophysiology of cancer. The human ether-á-go-go-related gene (hERG) can be considered one of the most critical ion-channel encoding genes involved in the establishment and maintenance of neoplastic growth. In this review, evidence is presented to demonstrate that hERG channels are frequently over- and/or mis-expressed in many tumour cell lines as well as in primary human cancers. Moreover, many tumour cells, especially leukaemia cells, express a truncated isoform (hERG1B) along with the full length hERG1 protein, to form heterotetrameric channels. Three main functions relevant to tumour cell biology can be ascribed to hERG channel activity: (i) the control of cell proliferation, especially in leukaemias; (ii) the regulation of tumour cell invasiveness, possible through a physical and functional interaction with adhesion receptors of the integrin family; and (iii) the control of tumour cell neoangiogensis, through the modulation of angiogenic factor secretion. hERG channels are thus considered novel diagnostic and prognostic factors in human cancers, as well as targets for anti-neoplastic therapies.