IgE-mediated cow's milk allergy (CMA) is a heavy burden for patients, particularly for children and their families. Allergen avoidance represents the only therapeutic option, but oral desensitization protocols have been suggested. Because of the long duration and complexity of these protocols we examined the feasibility of an oral tolerance induction protocol using a weekly up-dosing schedule. Children with IgE-mediated food allergy to milk, confirmed by a double-blind placebo-controlled food challenge, were recruited. Six of them were randomized to double-blind desensitization with milk or soy formula as placebo. Seven patients underwent the protocol in open fashion. The desensitization schedule started with one drop of whole CM diluted 1:25 every week. The dose was doubled weekly until the 18th week to achieve an intake of 200 mL in approximately 4 months. Of the 13 children enrolled, 10 children received CM and 3 control children received soy formula. Full tolerance (200 mL of milk) was achieved in 7 children; in 2 children this therapeutic approach failed, because severe reactions occurred during the procedure. One patient achieved a partial tolerance (64 mL of milk). The three control children receiving placebo still showed a positive food challenge at the end of the study. A weekly up-dosing oral tolerance induction could be a viable alternative to traditional protocols for children with IgE-mediated CMA.