The epidermal growth factor receptor (EGFR) is a rational target for cancer therapy because it is commonly expressed at a high level in a variety of solid tumours and it has been implicated in the control of cell survival, proliferation, metastasis and angiogenesis. However, despite evidence to suggest that EGFR expression is associated with a poor prognosis in some tumours (e.g. breast, head and neck carcinomas), the situation is by no means clear-cut. A number of issues are worthy of particular consideration, including how EGFR is measured and whether these assays are sensitive and reproducible, which mechanisms other than increased EGFR expression might cause the EGFR signalling drive to be increased, and the relationship, if any, between EGFR expression and the response to EGFR-targeted agents.