BACKGROUND In outpatient clinics for neuromuscular diseases sometimes patients are presented because of an raised activity of the serum creatine kinase (CK) activity, accidentally detected. The purpose of this study was to investigate, how many patients with an unexplained hyperCKemia really suffer from a neuromuscular disease, and to present an adequate procedure for evaluating pathological CK activities. METHODS In this retrospective study, clinical, electromyographic and myopathological findings of 100 consecutive patients (38 women and 62 men, aged 19 to 78 years) with such an abnormality of unknown origin are presented. RESULTS Only 41 patients really had no muscular troubles and no signs of neuromuscular disorders at physical examination. The CK of 12 patients turned to normal at follow-up examination. In 4 patients a so-called makro-CK was found. In 50 patients, in-depth examinations including a muscle biopsy were performed. In 10 patients, the increased CK-activity could be attributed to a complication of an already known basic disease, e.g., by confirming a myositis in case of proven connective tissue disease. In 14 patients an independent muscle disease was proven: 3 degenerative, 5 metabolic or mitochondrial as well as 4-inflammatory myopathies. In 2 patients, a secondary myopathy in polyneuropathy was suspected to be the etiology of the increased CK activity. In 9 patients, well treatable disorders were discovered. In 34 patients, no muscle biopsy was performed and follow-up examinations were recommended. The ratio of the clarified diagnoses did not depend on the level of the CK activity. CONCLUSIONS Every hyperCKemia indicates a thorough internal and neurological examination independently from the level of the enzyme activity. A scheme for examination in case of abnormal CK activity is proposed.