441 Background: Current guidelines emphasize the use of CT or MRI for hepatocellular carcinoma (HCC) diagnosis, with strict regulation of biopsies. However, Hepatocellular-Cholangiocarcinoma (cHCC-CC), a liver cancer variant displaying histological elements of both HCC and cholangiocellular carcinoma (CCC), typically exhibits radiological features of both HCC and CCC on imaging studies. Additionally, platinum drugs represent the most promising initial treatment option for patients with unresectable or advanced cHCC-CC, deviating significantly from the treatment approach for HCC. Consequently, our study aims to assess the efficacy of imaging techniques in distinguishing between HCC, CCC, and cHCC-CC, highlighting its clinical significance. Methods: We conducted a database search to identify patients diagnosed with HCC, CCC, and cHCC-CC from June 2010 to September 2020. After implementing quality control measures, our study comprised 68 MRI scans from patients, including 30 with HCC, 23 with CCC, and 15 with cHCC-CC. Histological evidence confirming the diagnoses was obtained within a maximum of four weeks before or after the MRI scans. Subsequently, seven radiologists from Asia, Europe, North America, and South America, including abdominal imaging experts (AIEs) and non-abdominal imaging experts (NIEs) or trainees, independently and blindly assessed the MRI scans. They evaluated various MRI features and established a differential diagnosis encompassing HCC, CCC, and cHCC-CC. Results: The AIEs demonstrated high proficiency in utilizing MRI images exclusively for diagnosing HCC (70%-100%) and CCC (73.9%-91.3%). They significantly outperformed NIEs/trainees (all p values < 0.01), achieving accuracy rates of 26.7%-66.7% for HCC and 21.7%-60.9% for CCC. However, their ability to accurately distinguish cHCC-CC (6.7%-53.3%) was limited and comparable to NIEs/trainees (26.7%-46.7%). Additionally, there was greater consistency in MRI feature assessment among AIEs for HCC and CCC when compared to cHCC-CC. Notably, no significant differences were observed in the impact of a cirrhotic background on the diagnosis of HCC and cHCC-CC among AIEs. Furthermore, there was no significant intercontinental variability in overall liver cancer diagnosis and the diagnosis rates of the three types of liver cancer by AIEs. Conclusions: MRI imaging demonstrated effective differentiation between HCC and CCC, especially when interpreted by experts in abdominal imaging. Nevertheless, the ability to accurately detect cHCC-CC was notably constrained across all participating radiologists. Consequently, liver biopsy continues to play a pivotal role in ensuring diagnostic precision and facilitating the selection of appropriate medical treatment strategies.