Purpose Lysozyme, obtained from egg white, is a potential food allergen used in the dairy industry to prevent late blowing of the loaf caused by the outgrowth of clostridial spores (Cl. butyricum and Cl. tyrobutyricum) during cheese aging. The aim of this study was to evaluate the possible correlation between egg protein allergy in paediatric age and sensitization to egg lysozyme, used for the preparation of Grana Padano cheese. Methods The tolerability of Grana Padano cheese has been evaluated in paediatric patients allergic to egg proteins through an oral provocation test with increasing amounts of cheese containing, or not, lysozyme at 12 months and 24 months of aging. Results When lysozyme sensitized children received 12-months aged and lysozyme-containing cheese, several immediate and late adverse reactions such as itching, abdominal pain, vomiting, nausea, dermatitis, rhinitis, bronchial asthma, urticaria, angioedema, were seen in 5 out of 21 subjects; only 1 out of 21 children showed an adverse reaction after challenge with 24-months ripened lysozyme-containing cheese. Conclusions There is a possible relationship between the severity of allergic reactions and the lysozyme-specific IgE level in blood. In particular vomiting, hypotension and abdominal pain were present when IgE level was higher than 7 kU/L. A ripening time of 24 months may reduce allergy problems when lysozyme-containing cheese is given to sensitized subjects, probably due to the hydrolysis of antigenic epitopes during aging.