Abstract Background To minimize the risk of accidental reactions, atopic children with multiple sensitizations to tree nuts are advised to avoid all nuts. Multiple food challenges would be needed to confirm the clinical relevance, but are too burdensome to be practical. The usefulness of open mixed nut challenges in terms of safety, reactions during challenge, tolerance of the challenge material, effect on the elimination diet and satisfaction of the parents was evaluated. Findings Open mixed nut challenges were performed in 19 children with a previous negative hazelnut challenge and long term elimination diet for tree nuts. Challenges were negative in 13 (68 %) children, in four (21 %) children (non-severe) allergic symptoms were observed. The challenges were well accepted, safe and efficient. We were able to avoid multiple nut challenges in 15 (79 %) children. Conclusions Open mixed nut challenge can efficiently exclude multiple tree nut allergies in children with a lifelong nut free diet and low suspicion of clinical allergy.