Background: Material/Methods: Results: Conclusions: The treatment of complex tumors in non-functioning renal transplants requiring surgical extirpation is challenging. Here, we report the largest series of patients who underwent transplant radical nephrectomy for renal cell carcinoma (RCC) and transplant radical nephroureterectomy for urothelial cell carcinoma (UCC) in their transplanted kidneys. From 2004 to 2018, 10 patients underwent transplant radical nephrectomy (7 patients) and nephroureterectomy (3 patients). Retrospective analyses, in terms of complications, oncological recurrence, and survival, of peri-operative and long-term outcomes, were performed. Out of the 10 patients, 7 had RCC and 3 had UCC. No intraoperative mortality occurred. Three patients presented with Clavien-Dindo grade IIIa or greater within 30 days of surgery. Two patients died within 60 days of surgery, both due to vascular events: one due to myocardial infarction and one due to stroke. Two other patients died: one after 2.9 years, due to myocardial infarction, and the other after 6 years, due to unknown reasons. At the 7-year follow-up, there was a 60% overall survival rate. For all patients, average survival post-nephrectomy was approximately 4.5 years, including the 6 living patients and 4 deceased patients. Importantly, there was no observed cancer recurrence. This study reports outcomes of the largest series of transplant radical nephrectomy and nephroureterectomy for malignancies of renal allografts. In the optimized setting, extirpative surgeries appear safe, with favorable long-term oncological and survival outcomes.