No criteria exist for the modern diagnosis of Gianotti-Crosti syndrome (GCS). Our study objectives were to determine diagnostic criteria for GCS and to assess their validity using a prospective case-control design. We reviewed the clinical features of children with GCS who were reported in the literature from 1996 to 2000 and proposed a set of diagnostic criteria. We documented clinical features of children younger than 18 years who were diagnosed over a period of 18 months as having GCS and of control subjects given (over the same period) differential diagnoses of GCS. Forty-two children were recruited (11 with GCS and 31 controls with differential diagnoses of GCS). All children with GCS, and none of the controls, fulfilled the set of diagnostic criteria as a whole. We conclude that the proposed criteria are practical valid criteria for diagnosing GCS.