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Background: De novo cancers are feared complications after heart or lung transplantation. Recent data suggest that diabetes mellitus (DM) might also be a risk factor for cancer. We hypothesized that transplanted diabetic patients are at greater risk of developing cancer compared to non-diabetic ones. Methods: We reviewed 353 patients post-heart and/or -lung transplantation from our center between October 1999 and June 2021. Patients with follow-up <180 days (n = 87) were excluded from the analysis. The remaining 266 patients were divided into patients who had preoperative DM (n = 88) or developed it during follow-up (n = 40) and patients without DM (n = 138). Results: The diabetic cohort showed higher rates of malignancies in all patients (30.33 vs. 15.97%, p = 0.005) and in the matched population (31.9 vs. 16.1%, p < 0.001). There were also significantly more solid tumors (17.9 vs. 9.4%, p = 0.042; matched: 16.6 vs. 9.1%, p = 0.09) The presence of diabetes was associated with a 13% increased risk of cancer when compared to non-diabetic patients. New-onset post-transplant diabetes doubled the likelihood of cancer development. Conclusions: Pre-transplant diabetes mellitus increases the risk of cancer after heart and/or lung transplantation. However, new-onset diabetes after transplantation is associated with a much greater cancer risk. This information is relevant for screening during follow-up. [ABSTRACT FROM AUTHOR]