EditorialHepatoblastoma (HB) is the predominant form of pediatric liver cancer, usually arising in young children under 3 years of age [1], but it is a rare pediatric cancer with a very low worldwide incidence (<2 cases per million children under 18 years) [2]. Hepatocellular carcinoma (HCC) can also be diagnosed in children but with much lower incidence, usually found in the teenage population in association with predisposing conditions, such as the presence of underlying liver diseases (i.e., tyrosinemia and several cholestatic syndromes). As compared with HB, the prognostic of HCC is often poorer. A third type of primary liver cancer that appears at the late childhood and adolescence was initially called transitional liver cell tumor (TLCT), because it has a mixture of histological patterns characteristic of HB and HCC [3]. This cancer has been recently classified in a new provisional category named hepatocellular neoplasm not otherwise specified [4], awaiting for a better characterization, in an international symposium aiming to develop a consensus classification system for pediatric liver malignancies.Overall survival of patients with HB has notably improved from 30% in the 1970s to 70-80% nowadays thanks to the incorporation to the treatment of adjuvant and neoadjuvant chemotherapy using cisplatin and doxorubicin combined with efficient surgical approaches, including liver transplantation [5]. However, there are very limited treatment options for patients suffering from immature, invasive, and metastatic HB resistant to conventional first-line chemotherapeutic protocols, being the survival of these patients usually less than 3 years. The International Childhood Liver Tumor Strategy Group (SIOPEL) defined a prognostic stratification system of HB patients taking into consideration PRETEXT stage, metastatic disease, serum α-fetoprotein levels, multifocality, age and histology characterized by small undifferentiated cells [6]. Importantly, a recent study of the Children's Hepatic tumors International Collaboration (CHIC) group has confirmed these prognostic risk factors and identified new ones through a large-scale analysis using an extensive database including 1605 HB cases [7]. Patient stratification and treatment taking into account molecular biomarkers are the future challenges facing clinicians. High-throughput molecular studies of aggressive tumors highly refractory to anticancer drugs have the unique potential to provide a rational basis and new tools (biomarkers/molecular targets) for improving patient stratification and defining more specific and molecular-based therapies.Because HB is a rare tumor, most of the few existing studies have been carried out in small groups of patients, and this fact, together with the existence of several histologic subtypes without a clear consensus for their classification, has hindered advances in the characterization of different aspects of this liver cancer. Histologically, HB is usually composed of combinations of epithelial, mesenchymal, undifferentiated and other ...