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We describe a case of granulomatous slack skin in a 31-year-old woman with an unusual presentation of acquired ichthyosis and muscular masses involving four limbs over 3 years. Vesicles and ulcerative skin nodules first appeared only 3 months prior to diagnosis. The diagnosis was confirmed after sequential biopsies of muscle, skin lesions, and lymph nodes, together with molecular genetic studies. The patient responded poorly to various therapies, including thalidomide, and died of doxorubicin-related cardiomyopathy.