A case of cystic adventitial disease (CAD) of the popliteal artery with intermittent claudication in the left calf is reported. This patient was first treated by total excision of the cyst and the involved artery followed by graft interposition with an autogenous saphenous vein. Recurrence of CAD in the interposed vein graft was noted after 6 months, and excision of the cyst with the involved graft and graft interposition with an autogenous saphenous vein was again required. We consider that the definitive evidence from early recurrence in the interposed vein graft shown in this case will close the discussion of the cause of CAD. The cystic lesion is thought by some to originate from the adventitia; traumatic, embryologic, or systemic abnormality theories were proposed. We assume that the mucin-secreting synovial cells originating from the neighboring joint capsule, tendon sheath, or, in some cases, from the ganglion itself, directly invade the adventitia through any rough or injured crack caused by trauma to the adventitia or simply attach to and encircle the adventitia. Total resection of the lesion with grafting is the recommended treatment for CAD because of the excellent results. However, as shown in our case, complete removal of the synovial cells even by resection technique may be difficult; therefore intensive follow-up is fundamentally necessary in this disease.