Background: Necrolytic acral erythema (NAE) is a distinct skin entity and is strongly associated with chronic hepatitis C virus (HCV) infection. It is distinguished by its acral location, typical clinical and histopathologic features, and positive serum antibodies against HCV. Most cases have been treated with variable success using oral zinc, amino acids, and interferon with or without ribavirin therapy., Methods: We report two patients with the clinical and histopathologic features of NAE; however, both tested seronegative for HCV. Both patients were treated with oral zinc acetate with good response, with one showing a partial relapse after stopping oral zinc. The clinical features, histopathologic findings, association of HCV, and treatment of NAE in different case reports were reviewed., Conclusion: NAE has a strong association with HCV, particularly in prevalent countries such as Egypt. Nevertheless, it may occur independently without HCV association, and oral zinc may prove to be a less toxic therapeutic option for such cases.