Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. No effective systemic treatment has been established, except for sorafenib chemotherapy. In fact, sorafenib has proved to provide a statistically significant survival extension of about two months in two phase III trials in the North America-Europe area and in the Asia-Pacific area, which respectively reported a median survival after treatment of 10.7 and 6.5 months, respectively. We report the case of an HCC patient, who received a four-month therapy with sorafenib with a clinical, biochemical and radiographic response, but had to interrupt treatment because of a myocardial infarction. Surprisingly, despite no antitumor treatment having been administered for about a year, the patient has shown no tumor progression and is currently on a close follow-up. Should other similar cases be presented, a subset of patients with long-lasting response to sorafenib might be identified.