The primary purpose of this study was to develop methods to estimate cancer risk among those with sickle-cell disease (SCD) in California. SCD is an inherited disorder of hemoglobin. Increased hematopoietic cell turnover, chronic inflammation, and reduced immune function have led to speculation that cancer risk may be higher in this group. Despite this conjecture, there is a dearth of population-based studies on cancer risk among those with SCD. In this study, we utilized California's Office of Statewide Health Planning and Development (OSHPD) hospital patient discharge (PD) and emergency department utilization (ED) data systems to identify individuals with SCD. Cases coded as ICD-9-CM 282.60, 282.61, 282.62, 282.63, 282.68, 282.69, 282.41, or 282.42 from any of the 25 diagnostic fields were captured, from 1991-2007 from the PD or 2005-2007 from the ED data systems. A case was excluded if the patient's Social Security number was deemed nonsense; SCD was coded as a comorbid condition for a single visit; or the patient's age was less than 2 years. The resulting SCD case cohort was linked to the California Cancer Registry (CCR). Disease prevalence was estimated for 2006 mathematically using a formula consisting of the cohort sum; SCD live births and deaths from 2005-2007. We identified 152,369 SCD-related admissions to California hospitals and/or emergency departments from 1991-2007. Of those, 9,066 admissions were among patients whose SSN was deemed nonsense and 3,047 among children less than 2 years old. Of the remaining patients, 1,370 had only 1 admission with a comorbid SCD diagnostic code. The final cohort consisted of 7,144 persons, which was linked to the CCR, 1988-2007. We found 203 patients with 216 tumors. We estimated the prevalence of SCD in California, for 2006, at 3,633 individuals. This is the first study to use both California OSHPD PD and ED data systems in concert for SCD case finding and to estimate SCD prevalence in California based on healthcare utilization. It is also the first time that a SCD case cohort has been linked to the CCR to ultimately determine cancer risk in this population.