By eliciting distinct transcriptional responses, the oestrogen receptors (ERs) ERα and ERβ exert opposite effects on cellular processes that include proliferation, apoptosis and migration and that differentially influence the development and the progression of cancer. Perturbation of ER subtype-specific expression has been detected in various types of cancer, and the differences in the expression of ERs are correlated with the clinical outcome. The changes in the bioavailability of ERs in tumours, together with their specific biological functions, promote the selective restoration of their activity as one of the major therapeutic approaches for hormone-dependent cancers.