Complete removal of the tumor (R0 resection) is one of the most important prognostic factors for overall and recurrence-free survival in patients with hepatobiliary malignancies. Accordingly, the intraoperative confirmation of tumor-free resection margins is of central importance. At the same time, despite extensive preoperative diagnostics intraoperative findings can arise that require immediate histological clarification. For example, the discovery of peritoneal carcinomatosis or previously unknown intrahepatic metastases often leads to the termination of the operation and thus to a change in the oncological concept. In addition, the estimation of the local tumor spread, particularly in the case of biliary tumors related to the liver hilum, is sometimes difficult based on preoperative imaging, so that a timely intraoperative assessment of tissue samples is necessary to confirm the resectability. The possibility of intraoperative frozen section diagnostics is, therefore, of particular importance, especially in complex surgical interventions in the hepatobiliary area.