Hepatocellular carcinoma with bile duct thrombosis is a subtype of hepatocellular carcinoma, whose pathology is characterized by the growth of hepatocellular carcinoma cells in the liver parenchyma while metastasizing into the adjacent bile ducts and causing different degrees of obstruction of the biliary system. Due to the presence of bile duct cancer thrombus, these patients will also have typical clinical manifestations of biliary tract diseases, so they are very easy to be misdiagnosed as other diseases of the biliary system. Misdiagnosis will lead to the wrong design of surgical plan, which will seriously affect the treatment effect. Recent data from Eastern Hepatobiliary Surgery Hospital shows that the most easily confused diseases with hepatocellular carcinoma with bile duct cancer embolus are cholangiocarcinoma of the hilar region and biliary adenocarcinoma of the lower bile duct (including mucinous papillary adenoma/carcinoma of the bile duct), followed by bile duct stones. Therefore, the above two are the focus of differentiation. How to more accurately diagnose hepatocellular carcinoma with bile duct adenoma/carcinoma has become an important proposition for every hepatobiliary surgeon specialist. The clinical symptoms of biliary obstruction caused by bile duct adenoma/carcinoma or bile duct stone are similar to those of biliary obstruction caused by bile duct cancer embolism, both of which can manifest as rapid increase of yellow staining of skin and sclera in a short period of time, so it is very difficult to differentiate from clinical symptoms alone. Some patients with cholangiocarcinoma embolism can also be combined with biliary tract infection, which can be easily confused with acute biliary tract infection caused by bile duct stones. Only by combining the patient’s medical history, perfecting serological tests and carefully analyzing the subtle differences in imaging examinations can we make a correct judgment. The majority of patients with hepatocellular carcinoma with bile duct embolus have hepatitis B or C virus carriage or infection, and most of them have elevated alpha-fetoprotein (AFP). Among imaging examinations, ultrasound is the best method to distinguish bile duct cancer emboli from bile duct stones, but is less effective in distinguishing bile duct cancer emboli from bile duct adenoma/carcinoma. Most ultrasound examinations of bile duct emboli show flocculent echogenicity without posterior acoustic shadowing, whereas bile duct stones appear as strongly echogenic clusters with posterior acoustic shadowing on ultrasound. Energy-spectrum CT and MRCP can better differentiate hepatocellular carcinoma with bile duct thrombosis from bile duct adenoma/carcinoma. In contrast, the bile duct wall of patients with hepatocellular carcinoma with bile duct thrombosis is smooth and does not show thickening and stiffness. However, because the bile duct cancer thrombus is relatively soft and rarely grows infiltratively, the bile duct cancer thrombus is usually long and shuttle-shaped or cast along the bile duct, and there is a small amount of bile distribution between the bile duct wall and the gap between the thrombus tissue and the bile duct wall. The key points of differentiation between hepatocellular carcinoma with cholangiocarcinoma embolus and the most frequently misdiagnosed diseases are summarized here (see Table 1), in the hope of improving the diagnostic accuracy of hepatocellular carcinoma with cholangiocarcinoma embolus. Table 1: Differentiation points of hepatocellular carcinoma with bile duct cancer embolus and common biliary tract diseases Bile duct adenoma/carcinoma Progressive deepening of skin, scleral yellow staining, rarely fluctuating, vague pain in right upper abdomen common in a few carriers or infected patients Not elevated Slightly elevated, slightly hypoechoic or flocculent echogenicity in bile ducts, no posterior acoustic shadow Thickening and stiffness of bile duct wall, irregular pattern, bile ducts adjacent to cancer site narrowing into cancer site Bile ducts surrounding adjacent cancer site narrowing into tumor, and irregular pattern Bile duct stones Severe pain in the right upper abdomen is common, with skin and sclera yellowing in a small number of patients, jaundice fluctuation is common A small number of patients with carriage or infection are not elevated Strong echogenic clusters in the bile duct with posterior acoustic shadow The bile duct wall may be thickened, but stiffness of the bile duct wall is rare Filling defect shadow in the bile duct, proton imaging filling defect shadow with very low signal