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Background: Hepatitis C viral infection is a significant public health problem; 170 million persons are infected worldwide and the prevalence in the southern part of the United States exceeds two percent. Extrahepatic manifestations of hepatitis C viral infection are common; notably, 15-20% of patients will develop cutaneous manifestations of their disease. There are numerous dermatologic diseases associated with hepatitis C infection, including lichen planus, leukocytoclasticvasculitis, and porphyria cutaneatarda. Main observation: Recently, epidemiological studies have also demonstrated an association between hepatitis C infection and the development of non-Hodgkin lymphoma, especially marginal zone B-cell lymphoma. Herein we report the unusual case of a systemic marginal zone lymphoma in a patient with hepatitis C infection presenting clinically as localized lipoatrophy. Conclusion: Lipoatrophy can be a rare and diagnostically challenging presentation of secondary cutaneous marginal zone B-cell lymphoma. The importance of early recognition and detection cannot be over emphasized, as new and effective anti-viral treatments can lead to lymphoma regression in up to 75% of patients. To our knowledge, this is the first case of hepatitis C viral infection associated marginal zone lymphoma to present as localized lipoatrophy. [ABSTRACT FROM AUTHOR]