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The serological pattern, "anti-HBc alone", characterized by the presence of antibodies against the core antigen of hepatitis B virus (anti-HBc) as the only marker of hepatitis B, is not rare in a diagnostic setting. Depending on the prevalence of HBV infection and the patient group investigated, 1-31% of positive anti-HBc results are isolated positive findings. Anti-HBc alone is frequently observed in intravenous drug addicts, HIV-infected individuals, patients who are coinfected with HBV and hepatitis C virus, and pregnant women. However, it is not clear how this profile should be interpreted. Several studies have shown that anti-HBc alone is not only compatible with acute and resolved HBV infection but also with chronic infection. The reasons for the lack of HBsAg and anti-HBs in anti-HBc-alone individuals are not clear, but several mechanisms and possibilities have been suggested that could explain this phenomenon, some of which are delineated in this article.