The panniculitides are a group of heterogeneous inflammatory diseases involving the subcutaneous fat, the pathogenesis of which is poorly understood. Here, we report on a female infant with Prader–Willi syndrome who developed a systemic inflammatory disorder in the neonatal period demonstrating recurrent panniculitis as a prominent feature. This is the second report of an association between Prader–Willi syndrome and panniculitis. Such an association might be explained by the unmasking of a recessive allele as a consequence of hemizygosity, in the case of a 15q11 deletion, or homozygosity, in the case of maternal isodisomy. © 2011 Wiley Periodicals, Inc.