Mycosis fungoides (MF), the most common form of cutaneous lymphoma is derived from postthymic T cells that migrate to the skin likely under the influence of chronic antigen stimulation. Less common histomorphologic variants are diagnostically challenging because of their resemblance to reactive conditions. Three men aged 46, 73, and 74 years and one 83-year-old woman were encountered in the files of one of the authors and represented the patients. The patients had a longstanding eruption for several years. In 2 cases, the clinical course was aggressive with extracutaneous lymph node and/or peripheral blood dissemination. One patient had vesicles noted clinically. In all cases, vesiculation was a prominent feature histologically, which lead to an erroneous categorization initially as a reactive process. Basilar colonization by cerebriform lymphocytes along with the mucinous quality of the vesicle was diagnostic clue histologically, whereas the phenotypic and molecular profile was typical for MF. Strong expression of interleukin 5 and interleukin 10 in atypical lymphocytes in comparison with interferon gamma suggested a T-helper type 2-dominant cytokine microenvironment. In reviewing the literature of the 6 previously reported cases, 3 patients died of the disease; all these patients had vesicular lesions both clinically and histologically. We concluded that vesicular MF is a distinct histological and in some instances clinical variant of MF. The correlation of the vesicular eczematous quality of the eruption and a more aggressive clinical course may reflect the skewing toward a T-helper type 2-dominant cytokine milieu typical of advanced disease.