Insulin-like growth factor II (IGF-II) is a protein hormone that has been shown to exert several biological functions in mammals. IGF-II is produced mainly by the liver and to be systemically released to affect both the liver, in an autocrine and paracrine manner, as well as other tissues, through endocrine signaling. Nevertheless, it is also produced locally in various other tissues acting via autocrine and paracrine signalling. Research over the last decades has suggested that IGF-II also has a stimulatory effect on tumour cell growth but there are some notable exceptions to this rule. This conflicting view may have several explanations and hence current research has focused on gaining further insight into the transcriptional regulation and the metabolic pathways of IGF-II, which is hoped will result in greater understanding of the role of IGF-II in tumour development and new cancer therapies. This article aims at reviewing some of the key findings on how IGF-II affects tumour cells in vitro, as well as in vivo.