Background Hypopigmented dermatoses, more evident in dark-skinned people, are a frequent cause of consultation. Their etiology includes a wide range of dermatoses, from benign to malignant diseases. The clinical presentation appears very similar between them, making the correct diagnoses and management a challenge. Methodology Clinical records and histopathological biopsies were identified and compared in patients of the "Dr. Manuel Gea Gonzalez" General Hospital throughout a 16-year period with the presumptive diagnosis of hypopigmented epitheliotropic T-cell dyscrasia (HTCD) or hypopigmented mycosis fungoides (HMF). Immunostaining analysis was performed in each specimen, the panel of antibodies used was: CD3, CD4, CD7, CD8, CD20, and CD62L. Results Thirty cases of 81 patients found in the registries were included in this study. The main age group was formed by children younger than 15 years old. The main clinical differences between both entities were gender, presence of plaques, and neck lesions. The most significant histopathological parameters used to differentiate both diagnoses were: severity of lymphocytic infiltration, the extent of epidermotropism, folliculotropism, presence of Pautrier's microabscesses, lymphocytes with cerebriform nuclei, and dermal fibroplasia. No immunohistochemical differences were found between them. Conclusion The clinical distinction between HTCD and HMF continues to be a challenge, therefore an extensive clinicopathological correlation must be performed. AbCD7 and AbCD62L were not useful to differentiate both dermatoses. This paper suggests that HTCD and HMF should be considered as the beginning and the end of the same clinical spectrum.