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Isolated agenesis of the gallbladder is a rare anomaly,often asymptomatic. However, one patient out of four presented with right upper abdominal pain, nausea, and fatty food intolerance. The condition is frequently mistaken with an excluded or sclero-atrophic gallbladder, regardless of the imaging modality used. Consequently, AG often leads to unnecessary and potentially dangerous laparoscopic surgery as described in a few case reports over the last10 years. The aim of this study is to clarify the diagnostic and therapeutic approach of this unusual pathology. Two cases seen in our institutions were retrospectively reviewed, together with a review of the American and European literature. During laparoscopy, the absence of normal anatomical structures and the impossibility of pulling on the gallbladder to expose and dissect the triangle of Callot increases the risk of iatrogenic injury to biliary or portal structures. Depending on the experiment of the surgeon in laparoscopic procedure, this has to be taken into account to decide a conversion to laparotomy.A high index of suspicion is necessary when interpreting the radiological images. In case of doubt, a MRJ-cholangiography is mandatory. Because of possible inherited transmission,relatives with a history of biliary symptoms should be investigated.