The mannose 6-phosphate/insulin-like growth factor-II receptor (M6P/IGF-IIR) is an intriguing protein with multiple ligands and multiple functions. Approximately 90 - 95 % of the receptor is located intracellularly, with 5 - 10 % being on the cell surface. It has long been known to play an essential intracellular role in the transport of newly-synthesized lysosomal enzymes from the trans-Golgi network (TGN) to the lysosomes. More recently, however, the loss of this receptor has been described in some tumour types, suggesting that it may play a role in tumour suppression. The focus has therefore shifted to elucidating the role played by the cell surface receptor and its interaction with its diverse ligands in tumour growth and progression. The list of ligands is continuously increasing and includes growth factors such as IGF-II and transforming growth factor beta (TGFbeta). This review will address the question of whether the M6P/IGF-IIR plays a direct role in tumour suppression or merely plays an indirect role as a transporter for ligands designated for degradation in the lysosomes.