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Surgical resection is the effective treatment modality for hepatocellular carcinoma (HCC); however, rapid recurrence of the tumors are frequently observed even after apparently curative resection. The recurrence and prognostic assessment of patients with HCC after resection is an important clinical issue. We recently reported that aberrant expression of Aurora B is observed in primary HCC, and that it can be a predictive factor for HCC recurrence exceeding Milan criteria after curative hepatectomy. In this study we investigated the expression of the newly observed Aurora B splicing variant forms in HCC, and their roles in hepatocarcinogenisis. The expression of Aurora B and splicing variant forms were screened in 125 HCC patients (94 chronic hepatitis with cirrhosis background liver specimens), 18 metastatic liver cancer patients and 16 normal liver specimens by cDNA microarray, reverse transcription – polymerase chain reaction (RT–PCR) and Real time quentitative Reverse Transcription PCR (qRT-PCR). The results showed that expression of Aurora B splicing variant 2 (AURKB-Sv2) variant form was absent in normal liver and was higher in metastatic liver cancer than HCC. This aberrant expression was associated with the advanced stages of HCC (P < 0.01), correlated with a poor outcome (P = 0.008) and short disease-free period (P = 0.018). Furthermore, AURKB-Sv2 variant form is associated with a higher level of serum α-fetoprotein, protein induced by vitamin K absence or antagonist-II (PIVKAII), tumor capsular invasion, multiple tumor formation and at an age younger than those with other variant forms (P < 0.05). The results thus suggest that AURKB-Sv2 variant form is more significantly associated with the advanced stages of HCC than others and is a marker of poor prognosis. Founded in the tumor capsular invasion and multiple tumor regions, suggests that this might play a role in enhancing multiple malignant tumor formation and recurrence of HCC in hepatocarcinogenesis. This is the first study to report clinicopathological significance of aberrant expression of AURKB-Sv2 variant form in hepatocellular carcinoma. (Cancer Sci 2009; 100: 472–480)