Immunosuppression may be etiologic for some skin cancers. We investigated the impact of human immunodeficiency virus (HIV) infection and solid-organ transplantation on skin cancer risk. We conducted a population-based case-control study among elderly U.S. adults (non-Hispanic whites, age 67 years or older), using Surveillance, Epidemiology and End Results Medicare linked data. The study comprised 29,926 skin cancer cases (excluding basal cell and squamous cell carcinomas) and 119,704 controls, frequency-matched by gender, age and calendar year (1987-2002). Medicare claims identified solid-organ transplantation or HIV infection before cancer diagnosis/control selection. As negative controls, we evaluated other medical conditions (e.g., hypertension and depression) and cancers (breast, colon and prostate) not linked to immunosuppression. Odds ratios (ORs) compared prevalence in cases and controls, adjusted for matching factors and number of prior physician claims. Risks of Kaposi sarcoma (N = 602) and cutaneous non-Hodgkin lymphoma (N = 1,836) were increased with solid-organ transplantation (OR [95%CI]: 11.06 [5.27-23.23] and 2.27 [1.00-5.15], respectively) and HIV infection (21.58 [11.94-38.99] and 2.41 [1.05-5.52], respectively). Solid-organ transplantation was also associated with increased risks of Merkel cell carcinoma (N = 1,286; OR [95%CI] 4.95 [2.62-9.34]) and other cutaneous sarcomas (N = 972; 4.19 [1.83-9.56]). Solid-organ transplantation was nonsignificantly associated with melanoma (N = 23,974; (OR 1.36 [95%CI 0.98-1.88]). Null or weak associations were observed for negative control medical conditions and cancers. Solid-organ transplantation and HIV infection were followed by increased risk for some skin cancer subtypes among elderly adults. These results highlight the potential role of immunity in development of skin cancers.