Surgery in patients with hemophilia is a serious challenge. It requires a comprehensive approach, as well as careful postoperative monitoring. We present here the first case of a transperitoneal laparoscopic radical nephrectomy (TLRN) for renal cell carcinoma, of the clear-cell type, performed in a hemophilia B patient. The level of factor IX clotting activity before surgery and on postoperative days 1-6 was maintained at 65-130% and at 30-40% on subsequent days until healing of the post-operative wound was achieved. The intraoperative and postoperative courses were uneventful. TLRN can therefore be considered safe and effective for renal cell carcinoma. In hemophilia patients, the TLRN procedure requires proper preparation, as well as adequate substitution therapy for the deficient coagulation factor provided by a multidisciplinary team in a comprehensive center.