Between 1952 and 1992, we identified 117 African Americans with renal cell carcinoma (RCC) at the University of Chicago. Three of these had sickle cell disease (SS) and 11 had presumed sickle trait (AS). Based on genotype frequencies, these represented a 16.7-fold excess of SS patients (p < 0.0001), but the incidence of AS patients was as expected. In addition, the median age for the SS patients at presentation with RCC (36 years) was significantly less (p = 0.04) than for the AS patients (55 years). We have found no prior reports of SS in RCC patients and suggest that chronic renal injury from sickling and possible immunosuppressive effects of multiple red cell transfusions may be risk factors. We also suggest the need to be aware of the possibility of RCC in SS patients who may have hematuria solely related to sickling.