A 63-year-old man bearing a palpable tumor had a lymph node metastasis adjacent to the sigmoid colon that was detected by computed tomography and positron emission tomography. The sigmoid colon and enlarged lymph nodes were surgically resected, and cancerous ascites were present. Pathologically, the tumor in the lymph node was a poorly-differentiated adenocarcinoma that was positive for CA19-9 as well as CK7(-/+), CK20(+/-), VEGF(+), p 53(+)and MIB-1 (>10%). We treated this case as a pancreatic or bile duct carcinoma due to the patient's markedly elevated serum levels of CA19-9 and SPan-1. However, we could not make a conclusive diagnosis. Gemcitabine-based chemotherapy was administered, and the patient had no signs of recurrence for 24 months after the operation. Then, a recurrence was identified by imaging studies, and the chemotherapy was changed to paclitaxel and carboplatin. The patient had stable disease until tumor regrowth was identified 38 months after the operation, chemotherapy was then stopped. However, at 48 months after the operation, the patient remains well and has no symptoms. Our case suggests that surgery and the appropriate choice of anticancer drugs may contribute to the long-term survival of patients with cancer of an unknown primary origin.