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Erythema multiforme major (EMM) is a hypersensitivity reaction usually secondary to medications, viruses or other infections. Its presentation is fairly typical with a symmetrical distribution of vesicles, bullae or targeted lesions on the upper body, arms, legs, palms, feet and oral mucosa. The authors present a delineated case of EMM in association with chronic lymphocytic leukemia (CLL) and non-Hodgkin′s lymphoma (NHL) with a very unusual clinical presentation evolving overtime into a unique, almost dermatomal distribution. Typical therapies were not initially helpful and intravenous immunoglobulin antibody had to be administered.