IgG4-related disease (IgG4-RD) is an emerging immune-mediated disease that can involve any organ. The involvement of the pancreas and biliary tract is the most common and well-studied in the literature. It is characterized by a non-specific presentation, mimicking a malignant process. The goal was to look at the different clinical and paraclinical aspects of this disease, as well as the challenges that come from its management. It was made up of three observations of patients with IgG4-RD involving the biliary tract and pancreas. The first observation concerned intrahepatic biliary cholangitis that was accompanied by portomesenteric thrombosis, which was discovered by cholestatic jaundice on the 15th day after an appendectomy, and the patient improved under corticosteroids and anticoagulants. The second observation concerned an acute revelation of the disease. It was an acute attack of chronic pancreatitis of IgG4-RD. The main symptoms were pancreatic pain and exocrine pancreatic insufficiency, and corticosteroid therapy allowed remission. The third observation was related to autoimmune pancreatitis (AIP) and IgG4-related sclerosing cholangitis, revealed by jaundice with cholestasis. The patient acquired corticosteroid resistance and an adverse progression to decompensated cirrhosis, and liver transplantation was indicated. The clinical presentation of IgG4-RD is heterogeneous, as evidenced by our three clinical observations. There are still significant gaps in our understanding, particularly in terms of pathogenesis and factors that influence therapy response. Further observational and interventional research is needed to better manage this disease.