Synchronous tumors of the pancreas and gallbladder are rare and often attributed to an abnormal pancreato-biliary junction, which results in a persistent reflux of pancreatic secretions leading to chronic biliary inflammation. We present the case of a 73-year-old woman with synchronous lesions of the pancreas and gallbladder initially considered as two primary localized cancers and treated with curative intent. At relapse, targeted next generation sequencing (NGS), performed in search of potential therapeutic targets, uncovered the fact that the two lesions appeared to be clonally related. This case illustrates the problem of synchronous lesions of the pancreas and gallbladder. New pathologic assessments with comparative molecular analysis of mutational profiles may be helpful in this context.