Early Detection Research Network (EDRN), a NIH supported initiative that has the responsibility for the development, evaluation, and validation of biomarkers for earlier cancer detection and risk assessment, will support a study supervised by Prof. G. Giannelli, University of Bari Medical School, by providing 600 samples to evaluate the diagnostic accuracy of biomarkers in liver cancer. SCCA-IgM among other biomarkers will be evaluated in two different phases. In phase I biomarkers performance will be assessed based on patients heterogeneity, to confirm that the heterogeneity observed in clinical practice in the HCC population might be explained by different etiologies, demographic, biological and pathogenetic characteristics. In particular the diagnostic accuracy of each proposed biomarker will be assessed in distinct etiological settings, such as alcoholic versus HBV, HCV; a single small nodule versus other conditions. In phase II biomarkers will be assessed for the clinical management of HCC, to see whether biomarkers can predict tumor progression, by assessing the longitudinal profile of the marker by a generalized multilevel model to evaluate repeated measures comparing biomarker values before and after therapy.