Impairment of liver function can be seen in cancer patients for a variety of reasons including metastasis, biliary obstruction, toxicity of chemotherapy or other concomittant drugs, can be paraneoplastic or can be due to infections, especially with hepatotropic viruses. Mostly reported in hematological malignancies, reactivation of hepatitis B virus (HBV) is a complication of chronic HBV infection in patients under cytotoxic or immunosuppressive therapy. Up to now, only a few cases of hepatitis B reactivation have been described in patients with solid tumors. We report an acute reversible deterioration of liver function tests following cytotoxic chemotherapy in an HBsAg-positive patient with metastatic pancreatic cancer due to hepatitis B reactivation. As far as we know, this is the first case of pancreatic carcinoma with reactivation following chemotherapy. As experience with acute flares of HBV carriers in solid tumors increases, the establishment of guidelines for the management of these patients has become more crucial.