The difficulties of differential diagnosis of generalized pustular psoriasis (GPP) and acute generalized exanthematous pustulosis are due not only to the similarity of skin rashes, but also to the variety of clinical forms of these pathological conditions. In most cases, medical history data can verify a diagnosis, but diagnostics is difficult when history taking is difficult or patients are forced to take long-term drug therapy, which excludes the possibility of determining the type of drug, causing the toxic reaction. These difficulties are most often found in elderly and senile patients, as well as in patients who are in resuscitation or intensive therapy units and are unconscious or with artificial lung ventilation. The rapid detection of systemic disease features, that is a typical GPP sign, requires timely examination or hospitalization of the patient suspected of GPP, which may not always be implemented in conditions of precise specialized medical care. The low informativeness of morphological study in the acute phase of GPP also does not always allow to make a differential diagnosis of generalized exanthematous pustulosis and to start therapy on time even in the hospital due to postponing clinical signs of disease.