Histopathological diagnosis of mycosis fungoides is difficult, especially in early lesions that may be indistinguishable from inflammatory dermatoses. Mycosis fungoides is a clonal proliferation of mature epidermotropic CD4+ lymphocytes. The aim of this study was to determine the contribution of the CD8-CD3 ratio to the diagnosis of mycosis fungoides. We retrospectively compared the immunophenotypic characteristics of 30 mycosis fungoides with 28 inflammatory dermatoses. The diagnosis of mycosis fungoides was reinforced in all cases by the presence of a cutaneous dominant T-cell clonal population. To analyze exclusively the lymphocytic infiltrates, CD4, which is also expressed by histiocytes, was not considered. The CD8-CD3 ratio was determined separately in the epidermis and the dermis using two methods, one quantitative and the other semiquantitative. Concordance rates between the two methods were higher in epidermal than dermal infiltrates. The mean CD8-CD3 ratio was significantly lower for mycosis fungoides than control cases, with the difference being greater in the epidermal than the dermal component. Although not absolutely specific, a low CD8-CD3 ratio in the epidermal component of a lymphocytic infiltrate supports the diagnosis of mycosis fungoides. It can be evaluated in routine practice using a semiquantitative approach.