There has been a significant increase in skin cancers in transplant patients in recent years. Transplant recipients are also more likely to develop skin cancers that are locally invasive with the potential to metastasize early. This study aimed to determine the effect of significantly reducing or stopping immunosuppressive therapy on prognosis of aggressive squamous cell carcinomas (SCC) in renal transplant recipients (RTRs). Retrospective study of nine patients with aggressive SCC identified two groups, one whose immunosuppressive therapy was not altered and the other who had their therapy stopped or significantly reduced. Aggressive SCC all occurred on the head and neck, with five of the primary tumors originating from the ear. Using a Wilcoxon-Breslow test to compare equality of survivor functions, reducing or stopping immunosuppression was associated with the prolongation of metastatic disease-free survival period (p=0.023). This nonrandomized pilot study suggests that reduction of immunosuppression in RTRs with aggressive SCC may improve prognosis compared to patients whose immunosuppression is unchanged. Allograft function may continue despite significant reduction of immunosuppression.