The main shortcoming of living donor liver transplantation (LDLT) in hepatocellular carcinoma (HCC) is the increased risk of tumor recurrence after transplantation which is mainly attributed to the lack of reliable selection criteria that can predict micro-metastasis. Many centers currently offer liver transplantation (LT) only to those patients fitting the Milan’s criteria. We report two cases where strict inclusion Milan’s criteria were applied but they developed fatal lung metastasis within 3 years following LDLT. The diagnosis of metastatic HCC was confirmed by fine needle aspiration (FNA) which showed moderately differentiated HCC in both cases. Surprisingly, in both cases there was no obvious involvement of the transplanted graft indicating that the micro-metastasis must have occurred before the LT. Both patients received FK-506 or cyclosporine in the lowest recommended doses. Therefore, we recommend that FDG-Positron Emission Tomography should be considered as a part of routine pre-transplant evaluation in an attempt to detect early HCC spread. CT chest should also be a part of routine post transplant follow-up to detect an early lung metastasis. Immunosuppression represents a risk factor for accelerated tumor growth; therefore immunosuppressant drugs should be reduced to the minimum effective dose. Tumor differentiation may reflect tumor aggressiveness and the subsequent risk of recurrence; therefore, pre-transplant FNA may help as an important test to predict the risk of recurrence. In conclusion, these 2 cases warrant a new strategy to detect early HCC spread, focusing on new immuno-histochemical or molecular biology techniques aiming to identifying new bio-humeral or pathologic factors reflecting the invasiveness of HCC.