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Oral allergy syndrome (OAS) is occasionally observed following consumption of raw fruits in allergic adults. Since this phenomenon was commonly reported in Khorasan province of Iran; we intended to check if common diagnostic tests could be applied for differential diagnosis of OAS to grapes. IgE reactivity of 84 patients with OAS to grape and 34 patients with OAS to other fruits were analyzed by in vivo and in vitro methods, and the results were compared with those of controls. The patients underwent skin prick test (SPT) with common allergic pollen extracts as well as grape extract. The specific IgE level to grape proteins was determined by an indirect ELISA. The correlation of SPT results with ELISA and western blotting patterns was checked by statistical methods. The results showed a significant correlation of grape SPT diameters with grape specific IgE levels. Furthermore, a significant association of grape SPT results with IgE immunoreactivity of a 10 kDa grape protein, probably lipid transfer protein (LTP) was prominent. Immunoreactivity of other proteins was linked with mild clinical symptoms. The study showed a significant correlation of grape SPT results with grape total extract, as well as its 10 kDa component’s IgE reactivity. The results suggested that OAS to grape should not be considered as a main criterion in diagnosis of grape allergy and a combination of grape SPT results with evaluation of IgE reactivity to grape 10 kDa allergen should be considered to achieve a more reliable grape allergy diagnosis.