The diagnosis of erythroderma is challenging, since clinical, histopathological and immunophenotypic findings are insufficient to differentiate between inflammatory and lymphomatous erythroderma. Thus, multiplex PCR was used for T-cell receptor-γ gene rearrangement analysis, in the skin and peripheral blood samples of 24 patients (20 men and 4 women) with erythroderma of varying origin, in order to estimate its diagnostic value. Cutaneous T-cell lymphoma was confirmed in 9, benign inflammatory dermatosis in 12, and idiopathic erythroderma and clonal dermatitis in 3 patients. In the group of patients with erythrodermic cutaneous T-cell lymphoma, the dominant clone was detected in the skin of 8/9, and in none of the patients with inflammatory dermatoses. A dominant clone was found in peripheral blood of 5/6 samples of patients with erythrodermic cutaneous T-cell lymphoma, and in 2/12 patients with inflammatory dermatosis. T-cell receptor-γ gene rearrangement analysis is valuable in differentiation between inflammatory and lymphomatous erythroderma, thus substantially improving the diagnosis of patients with erythroderma.