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The paper reports the case of a 12-year-old female affected by ulcerative colitis and treated with double immunosuppressant therapy (methotrexate and infliximab). The patient presented with 7 day-lasting fever associated with pharyngotonsillar hyperaemia, cheilitis, vesicular-bollous lesions on labial mucosa and rash on malar regions, chest and upper extremities. Since full blood count showed lymphocytosis and inflammatory markers were negative, a viral infection was suspected. Virological tests identified the presence of IgM against Cytomegalovirus (CMV), Herpes and Mumps viruses, but Real-Time PCR was negative for the DNA detection of any of those viruses. Despite hospital admission and different investigations, fever persisted for more than 7 days without any explanation. Therefore, it was considered as Fever of unknown origin (FUO). FUO is often an unusual manifestation of a common disease but so far there is not a single validated diagnostic protocol. In the presented case only did the repetition of the Real-Time PCR test after a few days enable CMV DNA to be identified in the patient's blood and urine and CMV infection to be diagnosed.