Isolated limb infusion (ILI) is a recently described minimally invasive technique indicated in the management of regionally advanced cancers refractory to systemic therapy and surgery. The present report describes the initial single-center experience of three patients with regionally advanced peripheral melanoma and one with lower-extremity cutaneous T-cell lymphoma treated over a period of 1 year. It is feasible to perform the complete ILI procedure in a single 60-100-minute session, solely in the interventional radiology suite, without a requirement for patient transfer to the operating room or extra waiting time between catheter insertion and chemotherapy infusion treatment.