AbstractHereditary persistence of alpha‐fetoprotein (HPAFP) is a rare benign autosomal dominant disorder. Here we report a 7‐year‐old healthy female who was found to have elevated alpha‐fetoprotein (AFP) of 55–88 ng/ml over a 2‐year period. Subsequently, AFP was also determined to be elevated in another 4 out of 8 family members in three generations, consistent with an autosomal dominant inheritance pattern. Elevated AFP levels are usually related to pregnancy, congenital disorders, liver diseases, or specific malignancies. However, HPAFP should be considered in the differential diagnosis of children with unexplained elevation of AFP. This disorder can be easily confirmed by measuring AFP levels in family members or checking specific point mutations of AFP gene promoter. Pediatr Blood Cancer 2009;52:403–405. © 2008 Wiley‐Liss, Inc.