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We evaluated the post-transplant course of the entire solid-organ-transplant population at our institution to determine the frequency, incidence and specific type of post-transplant malignancies which occured at a single center. Of 674 solid-organ-transplant recipients (305 renal, 307 heart, 54 lung, 8 heart/lung), we detected 79 malignancies (48 heart, 28 renal, 2 lung, 1 heart/lung), representing an overall cancer frequency of 11.7%, 15.6% for heart and 9.2% for renal transplant recipients. The frequency in both transplant groups was higher than that reported previously in the multicenter data in the literature (about 6%); we also noted a shorter interval to malignancy (27 vs. 61 months). The most common malignancies overall were skin/lip carcinomas and post-transplant lymphoproliferative disorder (PTLD). The frequency of PTLD was higher in non-renal (6.5%) than renal (0.7%) transplant recipients and statistical analysis confirmed a significant higher incidence of all malignancies (p=0.0032) and of PTLD (p=0.0001) in heart and lung recipients as opposed to renal transplant recipients. The frequency of total skin/lip carcinomas was essentially equal in the heart and renal transplant groups (6%), and statistical analysis showed no significant difference in incidence of this general type of malignancy; however, there was a marked disparity in interval to squamous cell carcinoma (SCC) between renal and heart transplant recipients (27 versus 59 months). This was associated with an apparent increase in the rate of occurence of SCC after 60 months in heart transplant recipients, a finding not previously reported in the multicenter data in the literature. We did not demonstrate a significant effect of the withdrawal of prophylactic OKT3 from the immunosuppression regimen of heart transplant recipients on the incidence of all tumors, PTLD or skin/lip tumors.