Conflicting views about the diagnostic value of skin biopsy in the investigation of erythrodermic patients are extant. The objective of the present study was to establish the frequency with which a correct diagnosis can be based on histopathological assessment alone. This was achieved by comparison of the "blinded" microscopic diagnosis with the final diagnosis (based on combined clinico-pathologic parameters and response to therapy). In a retrospective review of 56 skin biopsies from 40 patients with erythroderma, we found a positive correlation between the pathological diagnosis and the final diagnosis in 66%; furthermore, when the microscopic characteristics observed in different diagnostic categories were assessed, these proved to simulate those seen in conventional manifestations of the various underlying diseases but tended to be subtle in the setting of erythroderma. We conclude that, despite the homogeneity of the clinical expression of erythroderma, diagnostic histopathological features of the underlying disease are retained in the majority of cases.