Despite the elevated prevalence of insomnia in cancer patients, there is a lack of brief validated instruments for the evaluation of this particular problem in this population. The goal of this study is to empirically validate the Insomnia Severity Index (ISI) and to evaluate its ability to screen insomnia in 1670 cancer patients. The results support the internal consistency and temporal stability of the ISI. Its two-component factor structure is clear and stable between different cancer diagnoses. The construct validity of that instrument is also supported by correlations obtained with various measures of sleep and one measure of quality of life. The ISI is also sensitive to therapeutic changes. A clinical cut-off score of 8 on the ISI is associated with optimal sensitivity and specificity for the detection of sleep difficulties. In conclusion, the ISI appears to be an excellent evaluation and screening tool in the context of cancer.