We report the second case of chromoblastomycosis caused by Exophiala spinifera; this is the first known case in the United States. Examination of biopsied tissue showed thick-walled, internally septated, chestnut brown muriform cells (sclerotic bodies) within multinucleated giant cells present in the dermis that were characteristic of chromoblastomycosis. The individual cells within the muriform cells disarticulated from the outer wall of the parent cell and from each other to form endoconidia within the outer walls of the parent cells. After fracture of the outer walls, the endoconidia were released. This unique process of endoconidial formation in vivo for the propagation of muriform cells was observed for the first time. Initial treatment with itraconazole and 5-fluorocytosine followed by treatment with itraconazole and heat resulted in marked improvement in the patient's lesions. This infection reiterates the fact that the dematiaceous fungus E. spinifera, a well-known etiologic agent of phaeohyphomycosis, can cause more than one type of infection and supports earlier observations that chromoblastomycosis and phaeohyphomycosis represent extremes of a continuum of infections.