The persistent sciatic artery (PSA) is a rare anatomical variant where the internal iliac artery and the axial artery of the embryo provide the major supply of the lower limb, the superficial femoral artery being usually poorly developed or absent. We describe an extremely large right PSA in a 79-year-old male cadaver during a medical gross anatomy course, with simultaneous existence of a hypoplastic superficial and deep femoral artery. The PSA, which was a continuation of the anterior division of the right internal iliac artery, entered the buttock through the greater sciatic foramen situated in the gluteal region laterally to the sciatic nerve and in the mid thigh medially to the same nerve, becoming in the popliteal fossa the popliteal artery. Neither the superficial nor the deep femoral artery had communication with the popliteal artery. Because the PSA in our study was the only blood supply to the lower limb, we present the embryologic origins and the clinical anatomy of this artery.