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Objective: the authors report their experience in the treatment of a case of Syndrome of Mirizzi (SM) that it simulates a cholangiocarcinoma. Experimental design: report of 1 case. Evaluation of the effectiveness of the treatment and 2 years follow-up. Setting: Operative Unit of General and Thoracic Surgery, Department of Surgical, Anatomical and Oncological Disciplines. Policlinico, University of Palermo. Intervention: surgical treatment of the suspicious neoplastic lesion. Results: complete recovery with “restitutio ad integrum”. Conclusions: the SM constitutes one important challenge from the diagnostic and therapeutic point of view, since it is not infrequent that the correct definition of this pathology is only intraoperative. The role of the videolaparoscopic cholecistectomy is not still well defined. To reduce the risks of lesion of the biliary tree during surgical intervention, also in case of diagnostic doubt, we propose an integrated approach of sequential type, with the exploration preoperative through ERCP and following surgical intervention.