On the Cover: Elevated levels of TGF-pidermal growth factor receptors (EGFR) have been shown to be significant predictors of disease-free survival in head and neck cancer patients. However, only about 10% of head and neck cancer patients with overexpression of EGFR determined by immunohistochemistry respond to molecular therapy. This indicates the limited capacity of the immunohistochemistry in predicting treatment success of these patients, as overexpression of EGFR may not correlate with its functional status. To address this, Kong et al. have exploited high-throughput fluorescence lifetime imaging microscopy to measure EGFR autophosphorylation by fluorescence resonance energy transfer (FRET). The images shown illustrate the lifetime maps of two tumor cores from exemplary patients. The tumor from patient 1 (upper panel) indicates no change in lifetime between control (not shown) and experimental with a FRET efficiency of 0%. The analysis of patient 2 (lower panel) indicates a decrease of the average lifetime with a FRET efficiency of 11% for this core; this is indicative of EGFR autophosphorylation. Analysis of multiple samples of head and neck tumours using tissue microarrays shows that high FRET efficiency, i.e. autophosphorylated EGFR, is correlated with worsening disease-free survival. We are currently applying this technique to assess the activation status of ErbB2 in breast cancer patients and to correlate its functional status with the prognosis of these patients. It is anticipated that this powerful approach could be exploited as a new, independent, quantitative prognostic factor in clinical decisions and cancer management. For details, see the article by Kong et al. on page 2834 of this issue.