We explored differences in prognostic ability for mortality of the established and validated Charlson comorbidity index with two other comorbidity indexes developed for this study. Our study was limited to persons diagnosed with HNCA between 1985 and 1993 in a database formed by a linkage of files from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program with Health Care Finance Administration Medicare files (n=9386). Adjusted relative risks (RR) and 95% confidence intervals (95%CI) for comorbidity index scores of 1 or more compared to 0 were (RR=1.50, 95% CI 1.43-1.68) Charlson index, (RR=1.53 95% CI 1.42-1.66) HNCA index, and (RR=1.49, 95% CI 1.32-1.68) ATC index, respectively. The Charlson and HNCA indexes displayed dose-response patterns (P-value for trend <0.0001). Although the ATC index appears promising, the HNCA and Charlson indexes had similar adjusted RR's, dose-response patterns, P-values, and chi-square scores and appear particularly well-suited to the measurement of comorbidity.