Stubbs et al.16 postulated the existence of an extracellular pH-stat as a homeostatic mechanism for pHe that would curtail excessive acid loading, and recent studies have suggested that the ability of cancer cells to modulate the set point of tumour pHe may be an evolutionary strategy to achieve a stable state favouring invasion in response to microenvironmental selection pressures.17,18 Several in vitro studies have suggested that the properties of CAIX fit it for a role as an extracellular pH-stat.12,17,19 No published study has yet directly demonstrated such a mechanism in vivo, however. Here, CA9 is linked to neoplasm.