Previous reports of cancer after kidney transplantation have been limited by small numbers of patients in single-center studies and incomplete ascertainment of cases in large registries. We examined rates of malignancies among first-time recipients of deceased or living donor kidney transplantations in 1995-2001 (n = 35 765) using Medicare billing claims. For most common tumors, e.g. colon, lung, prostate, stomach, esophagus, pancreas, ovary and breast, cancer rates were roughly twofold higher after kidney transplantation compared with the general population. Melanoma, leukemia, hepatobiliary tumors, cervical and vulvovaginal tumors were each approximately fivefold more common. Testicular and bladder cancers were increased approximately threefold, while kidney cancer was approximately 15-fold more common. Kaposi's sarcoma, non-Hodgkin's lymphomas, and nonmelanoma skin cancers were more than 20-fold increased than in the general population. Compared with patients on the waiting list, several tumors were more common after transplantation (p < 0.01): nonmelanoma skin cancers (2.6-fold), melanoma (2.2-fold), Kaposi's sarcoma (9.0-fold), non-Hodgkin's lymphoma (3.3-fold), cancer of the mouth (2.2-fold), and cancer of the kidney (39% higher). The rates for most malignancies are higher after kidney transplantation compared with the general population. Cancer should continue to be a major focus of prevention in kidney transplantation.