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Hepatitis B virus (HBV) infection is endemic in various parts of the world. A proportion of patients have resolved prior exposure to HBV, as evidenced by the clearance of circulating hepatitis B surface antigen and the appearance of antibody to hepatitis B core antigen (anti-HBc), which could produce protective antibody to hepatitis B surface antigen (anti-HBs). With time, anti-HBs in some patients may become negative. Such patients are described as having occult HBV infection or anti-HBc alone. In the context of immunodeficient patients, such as HIV patients or lymphoma patients undergoing immunosuppressive immunotherapy, the lack of protective anti-HBs may increase the risk of hepatitis B reactivation. Serum HBV DNA testing may be necessary in anti-HBc alone patients, to detect patients at a high risk of developing HBV infection allowing appropriate prophylactic management.