BACKGROUND AND OBJECTIVES: The purpose of this study was to develop a comorbidity index specific to Black Men with prostate cancer, because certain comorbidities and prostate cancer are particularly prevalent among this racial group. METHODS: This research used the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database to develop an index of comorbidity burden based on survival, and the presence/absence of comorbid illness in 2,931 Black males diagnosed with prostate cancer. Comorbidity burden was recognized using inpatient, outpatient, and physician claims for a 2-year period prior to the diagnosis of prostate cancer. We compared five different statistical models, each with two-way, three-way, and/or four-way interactions among the comorbidities, and selected the model with only two-way interactions as the optimal choice. We demonstrated the utility of refining the simplest model, with 27 comorbidity categories only, by adjusting for the number of different diagnoses within statistically significant categories.