OBJECTIVE: This investigation aimed at highlighting the cancer risk of recipients of kidney transplant in northern and central Italy. METHODS: Data on 2,120 kidney transplant recipients from Niguarda Ca' Granda Hospital Milan, or from Policlinico "A. Gemelli", Rome, were analyzed The period at risk of developing cancer (person-years, PY) was computed from 30 days after transplant to date of cancer diagnosis, or date of death, or date of re-entering dialysis, or date of last follow-up. Observed and expected numbers of cancer were compared through sex- and age-standardized incidence ratios (SIRs) and 95\% confidence intervals (CIs). The transplant attributable fraction (AF) of cancer cases and incidence rate ratios (IRR) were also computed. RESULTS: After 16.594 PY of follow-up (median flow-up: 6.8 years), 121 cancer cases were diagnosed (729.2 cases/10(5) PY). The SIR for all cancers was 1.9. Kaposi's sarcoma (KS) (27 cases observed, SIR = 82) and non-Hodgkins lymphoma (NHL) (18 cases observed a SIR = 6.4 were the most common cancers. Significantly increased SIRs were also noted for native kidney (11 cases observed SIR = 4.9), corpus uteri (6 cases observed SIR = 4.6), and liver (6 cases observed, SIR = 3.1). The transplant AF was 46.9%, largely due to KS (98.8%) and NHL (84.3%). Since SIRs decreased with increasing age, the transplant AF ranged from 73.2% below 45 years of age to 30.4% after 54. Among risk factors, area of birth strongly influenced the risk of KS, with a 3-fold higher risk in those born in the South of Italy as compared to those born in the northern part. CONCLUSIONS: Immune depression after kidney transplantation entails a two-fold increased overall risk of cancer, mainly related to cancers associated to a viral aetiology. Furthermore, our findings suggest the need to adopt a specific serological screening for the prevention of post-transplant KS in individuals born in southern Italy.