Past assessments of comorbidity indices have sought to recommend a single index that performs better than others. The authors used a multiple informants approach as an alternative method to simultaneously assess five indices of comorbidity. This approach provides a single estimate of the overall effect of comorbidity and evaluates the relation any individual index has to the outcomes of interest. Association of comorbidity with definitive primary therapy, discussion of tamoxifen, and receipt of tamoxifen was evaluated in a cohort of 830 older breast cancer patients enrolled at four geographically distinct centers in the United States from 1996 to 1999. The estimated adjusted effect of a unit increase in comorbidity on the odds of discussing tamoxifen therapy was 0.70 (95% confidence interval: 0.56, 0.88). An increase in comorbidity was not associated with receipt of definitive primary therapy (odds ratio = 0.94, 95% confidence interval: 0.79, 1.13) or receipt of tamoxifen (odds ratio = 0.96, 95% confidence interval: 0.72, 1.27). The multiple informants regression proved superior to separate regression models that included only one index. In analyses that require comorbidity adjustment and for which no single index is expected to be ideal, the multiple informants approach is an attractive alternative to selecting a single index and to other methods of using multiple indices.