To evaluate the relationship between the occurrence of contact urticaria in reaction to cow's milk in infants and the diagnosis of cow's milk allergy (CMA) established by supervised oral food challenge. In this cross-sectional study, we identified 184 children who had undergone 221 oral food challenge (OFC) at a CMA reference center between July 2015 and August 2019. Of these, 23 (12.5%) had a history of contact urticaria to cow's milk and underwent a total of 30 OFC. Baked cow's milk OFC were excluded, and 21 children were included in the study. All data from clinical history and allergy tests (serum-specific IgE dosages and skin prick test [SPT] with reconstituted cow's milk formula) were recorded on standardized forms. The challenge was conducted with reconstituted cow's milk formula in increasing volumes every 15-20 min. 24 OFC were performed; 13/24 (54.2%) for diagnostic purpose and 11/24 (45.8%) to evaluate cow's milk tolerance. Allergy tests were positive in 14 patients (87.5%). Positive oral challenge outcomes were identified in 7/24. One patient had a late flare of atopic dermatitis and five children presented with immediate urticaria (two generalized urticaria and three perioral urticaria). The median papule diameter was 6.5 mm in patients with a positive OFC and 3.75 mm in the negative group (P = 0.02). The occurrence of contact urticaria might be the only manifestation among infants sensitized to cow's milk with tolerance to oral ingestion. Reactions due to oral challenge were related to a larger wheal diameter on the SPT.