Malignant cutaneous lymphomas comprise a heterogeneous group of diseases according to clinical and morphological characteristics. This article discusses the possibility of developing lymphoma in patients with chronic dermatoses. We report our own clinical observations of two cases of transformation of long-term widespread psoriasis into the erythrodermic form of malignant cutaneous T-cell lymphoma (CTCL) or Sézary syndrome in patients with a history of carcinogenic factors (sun exposure, contact with chemicals in the workplace, frequent PUVA-therapy sessions, ultraviolet irradiation). Taking into account the difficulties of differential diagnosis of erythrodermic forms of CTCL with secondary erythrodermas associated with benign dermatoses, both conventional (clinical blood test, lymphocytogram, histologic examination of the affected skin biopsy sample) and modern (immunophenotyping of blood lymphocytes, study of the affected skin to identify monoclonal and polyclonal proliferative lymphocytes in skin biopsy samples) general principles of laboratory and instrumental methods for patient examination were presented. In addition, the authors noticed that examination of peripheral blood lymphocytes can be used as a diagnostic tool when the histologic examination of the skin is less informative (e.g., when symptoms of inflammatory process prevail over proliferative symptoms). The presence of more than 5% of lymphocytes with morphological features of nuclei typical of Sezary cells in the peripheral blood smears is suspicious for CTCL.