The aim of the study was to verify whether there is a relationship between Gianotti-Crosti syndrome and an allergic background in children. Twenty-nine children affected by Gianotti-Crosti syndrome were first screened for a large panel of microbiological examinations, including serological and cultural tests for viruses and bacteria. A causative agent was identified in only 10 cases (34.4%). In five cases a diagnosis of Epstein-Barr virus infection was made on the basis of significant titres of anti-Epstein-Barr virus antibodies (IgM) associated with constitutional symptoms (fever, pharyngitis-tonsillitis). Our data concur with several clinical studies demonstrating that Epstein-Barr virus is now the most common viral agent associated with Gianotti-Crosti syndrome. For allergic evaluation, a group of 59 age- and sex-matched children investigated for recurrent infections were used as controls. The presence of atopic dermatitis (24.1%) in those with Gianotti-Crosti syndrome was significantly higher (p < 0.005) than in the control group (6.8%). In addition, a more common family history for atopy was 51.7% vs. 31% (p < 0.027) and the percentage of patients with total IgE greater than +2 SD for age higher than in controls (27.6% vs. 13.7%), as was the percentage of specific IgE present (31% vs. 17.2%). These results indicate that atopy is significantly associated with Gianotti-Crosti syndrome.