At present, there is no effective treatment of metastatic hepatocellular carcinoma (HCC). Systemic interferon alfa (IFN-alpha) was found to be of some use in patients with inoperable HCC in two randomized trials. We report a case in which metastatic HCC was cured by systemic IFN-alpha 2b in combination with surgery. A patient developed two bilateral pulmonary metastatic HCC nodules 5 months after the resection of the primary HCC. He was treated with systemic IFN-alpha 2b. One lesion completely disappeared. The other lesion showed an initial response but became resistant to the IFN-alpha 2b therapy after reduction in dosage because of the side effects. This was resected in view of the absence of new metastases after 9 months of IFN-alpha 2b therapy. He remained free from recurrence at 59 months of follow-up. A rare, but reversible, complication of retinal cotton wool spots caused by IFN-alpha 2b occurred in this patient. IFN-alpha 2b is partially effective in treating metastatic HCC. The time for its administration can also serve as an observation period, which is vital in deciding whether definitive surgical treatment of any residual lesions is indicated.