A 66-year-old man presented to the emergency department for painful and pruritic ulcerative cutaneous lesions involving his back, nose, lips (Figure, A), and mucosal lesions involving his oral cavity and oropharynx. The lesions initially only involved his lips and nasal bridge, and appeared 5 months prior while he was living on a ranch in Mexico. The lesions did not respond to treatment with an unknown oral antibiotic. His medical history included hypertension treated with captopril and a remote history of psoriasis. Physical examination demonstrated several dry, crusted skin lesions with blistering and ulceration, and shallow erythematous ulcerations of his oral mucosa. Internal medicine, otolaryngology, and dermatology departments were consulted. Results of flexible fiberoptic laryngoscopy demonstrated erythematous and ulcerative lesions with surrounding leukoplakia involving the base of tongue, glossoepiglottic fold, lingual and laryngeal surfaces of the epiglottis, and aryepiglottic folds (Figure, C and D). A QuantiFERON-TB Gold test was obtained, and results were found to be positive. Serum antigen testing for blastomyces, histoplasmosis, syphilis, HIV, hepatitis B virus, hepatitis C virus, human herpesvirus 6, cytomegalovirus, Epstein-Barr virus, varicella zoster virus, human polyomavirus 2, and West Nile virus were performed, and all results were found to be negative. A biopsy of the skin lesion was obtained from the edge of the lesion found on the patient’s back (Figure, B). Enzyme-linked immunosorbent assay serological testing was subsequently performed, and results demonstrated elevated levels of antidesmoglein 1 immunoglobulin G (IgG) and antidesmoglein 3 IgG.