Neuroleptic malignant syndrome is an uncommon but dangerous complication of antipsychotic drugs, characterized by clinical symptoms that include hyperthermia, severe muscle rigidity, autonomic dysfunction, and altered mental state. Serum creatine kinase (CK) elevation occurs in over 90% of cases. Many diagnostic criteria sets for neuroleptic malignant syndrome have been proposed, all of which include hyperthermia and muscle rigidity as major symptoms, and serum CK elevation as either a major or minor symptom. In general, elevated CK occurs in the initial stage of neuroleptic malignant syndrome and corresponds temporally with the onset of muscle rigidity. However, in some exceptional cases, CK elevation and emergence of muscle rigidity do not appear in the same stage, making early diagnosis of neuroleptic malignant syndrome more difficult. Two rare cases of neuroleptic malignant syndrome are presented in which elevated serum CK and emergence of muscle rigidity did not occur in the same stage of neuroleptic malignant syndrome. An elevated CK level is common in the early stage of neuroleptic malignant syndrome, suggesting that serum CK elevation is a useful indicator for early detection of neuroleptic malignant syndrome. However, a definitive diagnosis of neuroleptic malignant syndrome must be determined from the presence of specific clinical symptoms.