Background: Pre-anesthetic evaluation is an important aspect of perioperative patient management. However, anesthesiologists often encounter challenges during anesthesia due to conditions that are not detected during pre-anesthetic evaluations.Case: Case 1 involved a 74-year-old female patient scheduled for cranioplasty and meningioma excision. Severe pancytopenia was detected during anesthesia. Cranioplasty was only performed, the surgery was terminated, and drug-induced pancytopenia was diagnosed and treated. The pre-anesthetic test results were normal, except for anemia. Case 2 involved a 71-year-old male patient who discovered large ecchymosis during general anesthesia preparation in the operating room for choledochal cyst surgery. Surgery was canceled to evaluate the bleeding tendency, and acquired coagulation factor VIII deficiency was diagnosed and treated. The pre-anesthetic tests were normal, except for prolongation of the activated partial thromboplastin time. Conclusions: Abrupt hematologic and hemostatic changes may occur during anesthesia even though pre-anesthetic evaluation findings are normal.