Patients suffering from Type I glycogen storage disease frequently develop hepatic tumors. Some of these were classified as carcinoma, with the majority of tumors representing benign adenomata. However, no evidence exists of malignant transformation of adenomata in these patients. Here, we describe the occurrence of a hepatocellular carcinoma in the adenomata-bearing liver of the elder of two sisters suffering from Type I glycogen storage disease at the age of 20 years, 6 years after the diagnosis had been made. Surprisingly, α-fetoprotein levels were normal throughout the entire course of this patient, whereas the younger sister had elevated levels despite the absence of malignant lesions. Thus, the clinical significance of α-fetoprotein remains unclear in both cases. Nocturnal feeding, although performed continuously over the 6 years after the diagnosis, had obviously failed to prevent the development of hepatic tumors in both patients.