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We report an 80-year-old man who presented with spontaneous regression of hepatocellular carcinoma (HCC). He complained of sudden right flank pain and low-grade fever.The level of protein induced by vitamin K antagonist (PIVKA)-Ⅱ was 1 137 mAU/mL. A computed tomography scan in November 2000 demonstrated a low-density mass located in liver S4 with marginal enhancement and a cystic mass of 68 mmx55 mm in liver S6, with slightly high density content and without marginal enhancement. Angiography revealed that the tumor in S4 with a size of 25 mm×20 mm was a typical hypervascular HCC, and transarterial chemoembolization was performed. However, the tumor in S6 was hypovascular and atypical of HCC, and thus no therapy was given. In December 2000, the cystic mass regressed spontaneously to 57 mmx44 mm, and aspiration cytology revealed bloody fluid, and the mass was diagnosed cytologically as class Ⅰ.The tumor in S4 was treated successfully with a 5 mm margin of safety around it. The PⅣKA-Ⅱ level normalized in February2001. In July 2001, the tumor regressed further but presented with an enhanced area at the posterior margin. In November2001, the enhanced area extended, and a biopsy revealed well-differentiated HCC, although the previous tumor in S4 disappeared. Angiography demonstrated two tumor stains, one was in S6, which was previously hypovascular,and the other was in S8. Subsequently, the PⅣKA-Ⅱ level started to rise with the doubling time of 2-3 wk, and the tumor grew rapidly despite repeated transarterial embolization with gel foam. In February 2003, the patient died of bleeding into the peritoneal cavity from the tumor that occupied almost the entire right lobe. Considering the acute onset of the symptoms, we speculate that local ischemia possibly due to rapid tumor growth, resulted in intratumoral bleeding and/or hemorrhagic necrosis, and finally spontaneous regression of the initial tumor in S6.