Dysplasia of the connective tissue, which is a genetically determined disorder of the formation and postnatal development, represents a significant problem for modern medicine due to its high incidence and potentially serious consequences. Clinical manifestations of connective tissue dysplasia vary widely, from increased skin extensibility to vascular anomalies leading to sudden death. Various nevi, in isolated form or as a part of various syndromes, represent a large group within the connective tissue dysplasia. One of the rare genetically determined syndromes is Buschke—Ollendorff syndrome, which belongs to a group of orphan diseases with autosomal dominant inheritance. The main clinical manifestations of the syndrome are common connective tissue nevi of the skin, detected in early childhood, and osteopoikilosis, more often diagnosed in adults. Rare manifestations of Buschke—Ollendorff syndrome include various defects and disorder of the nervous system (from impaired cognitive development to epilepsy). Diagnosis of the syndrome is based on a combination of certain symptoms, the main of which are connective tissue nevi and osteopoikilosis. In the case of incomplete syndrome, the diagnosis is based on molecular genetic study, which is not available to all patients due to its high cost. This clinical case illustrates the challenges in the diagnostic search and the ambiguity of the results obtained. The presented clinical case was discussed at the citywide Moscow Consilium with the participation of dermatovenerologists of Moscow and professors N.N. Potekaev, V.G. Akimov, V.N. Grebenyuk, A.N. Lvov, E.A. Baktaev, N.G. Korotskiy, O.V. Zhukova, V.A. Volnukhin.