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Currently, a significant portion of the food consists of multiple different ingredients. Soybean proteins have been widely used for production of these combined foodstuffs. Meanwhile, soy proteins may contain a wide range of allergens, and even, if present in small amounts, they can cause severe allergic reactions due to cross-reactivity. The aims of our study were to evaluate the prevalence of sensitization to soybean allergen components Gly m 4, Gly m 5 and Gly m 6, and to map their IgE cross-reactivity with homologous proteins of Bet v1-like proteins and cupin proteins in patients with atopic disorders. We have studied IgE’s to 112 allergenic components of plant and animal origin in blood sera from 54 patients with history of allergy, using the ImmunoCap ISAC method. The results were analyzed by means of MS Excel program using parametric statistical criteria. Results: In patients with atopic diseases, we have detected serum IgE to the rGly m 4 allergic component (5 patients out of 29; 17.24%). Frequency of sIgE detection to rGly m 5 (3 patients of 29; 10.24%) and rGly m 6 (1 patient of 29; 3.44%) was less pronounced. Cross-reactive sIgE was detected only to allergens of the Bet v1 superfamily. The strongest relationship was found between sIgE level to rGly m 4 and rBet v1 (R = 0.68; p = 0.001). Another IgE cross-reaction was found between soybean rGly m 4 and alder pollen rAln g1 (R = 0.681; p = 0.000). IgE antibodies to rGly m 4 may also cross-react with kiwi rAct d8 (R = 0.59; p = 0.001). We have also found a weak correlation between sIgE to soybean rGly m 4 and two hazelnut rCor a1 isoforms: rCor a 1.01 (R = 0.42; p = 0.023), and rCor a 1.04 (R = 0.39; p = 0.036). The IgE cross-reactivity profile of the soy allergens revealed in this study is important for improvement of testing strategy for the presence of causally significant allergens. This finding will help to avoid the development of hidden cross-reactions that trigger both oral and respiratory allergic processes in subjects with allergic pathology. Moreover, this will enable administration of optimal diets and develop technologies for development of hypoallergenic food products.