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The etiology of mycosis fungoides (MF) is uncertain, although infectious agents and other environmental exposures have been implicated. We describe what appears to be the first case in which both a husband and his wife were diagnosed with large-cell transformation of MF. After 10 years of having stage I MF, the wife developed tumors that showed sheets of large transformed cells with dysplastic nuclei on skin biopsies, leading to a diagnosis of transformed MF. Her husband was diagnosed 14 months later with transformed MF following a biopsy of his right arm and leg after a 15-year history of presumed psoriasis. The fact that this rare occurrence happened in a couple who had been married for more than 25 years points to a common environmental exposure. Future studies should aim to clarify the potential role of infectious agents, such as human T-lymphotropic virus I and II, cytomegalovirus, Epstein-Barr virus, and other environmental exposures, in the development of MF.