The differential diagnosis of erythroderma (cf. Figs. 3.​11, 14.​28, and 14.​29), which has numerous causes, can be difficult due to the fact that the clinical picture is the same regardless of the causative disorder. Hence the importance of history taking, especially regarding previous dermatoses (such as psoriasis or mycosis fungoides), as well as drugs taken. History of the disease must also be very precise; a localized onset with pruritus and oozing, preceding a secondary generalization, may, for example, suggest a secondarily generalized contact dermatitis.

Careful clinical examination sometimes allows identifying primary lesions that are characteristic of the initial dermatosis (e.g., typical papules of lichen planus). These lesions must be looked for and biopsied in order to establish diagnosis. Examination of the scalp and mucous membranes must not be omitted. Finally, clinicians should bear in mind that, regardless of the cause of erythroderma, this syndrome has consequences on the general health condition that can be life threatening. Consequently, some patients may need to be hospitalized in specialized dermatology departments.