The present study was undertaken to evaluate objective measures of the smoking status of head and neck cancer patients during the course of radiotherapy. This was done by conducting a weekly structured interview, and measurement of carbon monoxide in expired air and of serum concentration of cotinine, the major metabolite of nicotine. These methods were tested prospectively in a series of 20 patients with head and neck cancer treated with radiotherapy. The results showed significant differences in the levels of end-expired carbon monoxide as well as serum cotinine among the different self-reported smoking groups. Combining the two objective measures and the interview data, the study revealed that up to 50% of self-reported non-smokers were in fact smoking actively. Measurement of end-expired carbon monoxide levels was found to be a precise indicator of smoking in the hours preceding measurement. Serum cotinine was a valuable measure of true smoking status. Assuming that this assay reflects the true smoking status, sensitivity, specificity and positive predictive value of self-reporting in this patient population was 79%, 80%, and 92%, respectively. In research aiming to investigate possible relations between smoking and radiotherapy, it is recommended that patients' smoking status be evaluated objectively as a supplement to self-reporting, at least in the head and neck cancer patients.