Blastomycosis-like pyoderma is a proliferative tissue response with multifactorial etiologies that may mimic other inflammatory and neoplastic skin disorders. It often occurs on sun damaged skin of immunocompromised patients. We report a case of blastomycosis-like pyoderma in a patient with underlying metastatic medullary carcinoma of the thyroid receiving treatment with sorafenib (a multikinase inhibitor). Prior treatments were unsuccessful. Our treatment with oral acitretin resulted in significant improvement.