Erythema multiforme — a disease that is sometimes a clinical conjecture because it can be represented by a wide morphological range of skin and mucous membrane lesions. Etiological factors for the erythema multiforme are diverse, and still numerous studies have shown that herpes simplex virus (HSV) is one of the most common causes of disease development. The detection rate of HPV DNA in lesions during examinations using nucleic acid amplification techniques reaches 70%, which allows to identify a single form of disease associated with HPV in clinical practice — herpes-associated erythema multiforme (HAEM). We present the descriptions of clinical observations of patients with different clinical forms of HAEM — simple papular, vesiculobullous, as well as atypical pigmented, which, along with typical eruptions on the oral cavity’s mucous membrane, was represented by the formation of hyperemia foci in the rounded or oval form on the skin of torso, upper extremities, the central part of them acquired an unusual hyperpigmented character in dynamics, transforming into atypical 2-zone foci with indistinct boundaries. The presented clinical observations once again confirm the variability of HAEM clinical manifestations, as well as the importance of the study of medical history data and laboratory examination conduction using nucleic acid amplification techniques to identify HPV DNA in the presence of clinical manifestations allowing to determine this diagnosis.