Telangiectasia macularis eruptiva perstans (TMEP) is a rare, heterogeneous disease of mast cell proliferation. The variable clinical presentation of TMEP, coupled with its rarity, makes the recognition and diagnosis of this disease difficult and challenging for clinicians. The histopathologic findings with hematoxylin and eosin staining that distinguish TMEP from a normal skin biopsy can be so subtle that confirmation of the diagnosis with additional special stains (c-Kit, Giemsa, toluidine blue) is strongly recommended. We describe three cases that highlight the variable clinical presentation of TMEP. One patient experienced only a localized skin manifestation, another an aggressive clinical course with systemic involvement, and a third diffuse skin involvement with mild fatigue, muscle pain, and weight gain.