As it is well-known, during secondary syphilis, it is possible to observe a systemic involvement of the treponemal infection. The visceral localizations are rarely observed, and they usually present themselves as asymptomatic or with aspecific symptoms. This report concerns a case of a homosexual patient who referred to us in order to perform blood tests for the main sexually transmitted diseases (HIV, HBV, HCV, TPEIA). Moreover, he reported a history of palmo-plantar erythematous desquamative lesions, spontaneously resolved. For this reason all the serological tests for syphilis have then been performed. Once the diagnosis of recent syphilis was made, and the antibiotic therapy with penicillin begun, the patient reported to have fever, abdominal pain and diarrhoea. The gastroenterological consultation highlighted the presence of a chronic active granulomatous colitis, but excluded an inflammatory or autoimmune aetiology. Because of this findings, and also because of additional histopathological examinations of the colon, the diagnosis of recent syphilis with intestinal involvement was made. The present case report confirms, once again, how the nickname ''great imitator'' is appropriate for calling syphilis. It highlights moreover that, as the incidence of syphilis is arising, in the presence of intestinal symptoms of unknown origin in patients with a history of unprotected sexual intercourse, syphilis should always be comprised among the possible diagnoses.