BACKGROUND One of the most controversial problems for liver transplantation in patients affected by hepatocellular carcinoma (HCC) remains the lack of an oncologic staging system to predict cancer recurrence after liver transplantation (LT). We analyzed allelic imbalance (AI) in 19 microsatellites, and assessed the post-LT HCC recurrence risk. MATERIAL AND METHODS Seventy-one patients were included; 18 had tumor recurrence within 5 years post-transplant. Molecular analysis was done in the primary HCC and peripheral blood samples: a total of 19 microsatellites was used to assess AI. Specific AI was evaluated when outside of range value between 0.66 and 1.5. Based on data in the literature, we grouped the 19 microsatellites into 4 panels. We calculated the fractional allelic imbalance (FAI) to make comparisons between different panels including different subsets of microsatellites. RESULTS We report that AI was associated with HCC recurrence in 3 main loci (D3S2303, D9S251, and D9S254). Tumor recurrence was associated only with 2 specific panels with 9 microsatellites previously reported to be associated with high risk for HCC recurrence. Our data show that fractional allelic imbalance (FAI) index has good negative ability to predict HCC recurrence (Panel 2: negative predictive value of 95%). CONCLUSIONS AI analysis could have prognostic value in risk management of HCC recurrence after LT, especially for early recurrence.