OBJECTIVE: The detection of gene fusion events is important for the diagnosis and management of malignancies. In this study, we describe the validation of a next-generation sequencing assay for multiplex detection of gene fusions. METHODS: Based on previously described gene fusion events that occur in pediatric oncology, a custom anchored multiplex next-generation sequencing assay was designed to target 93 genes. RESULTS: A total of 24 previously characterized specimens were examined. Twenty specimens had 1 or more previously described fusion events, and 4 specimens were negative for fusion events. The accuracy across specimens was 100% (20 of 20 specimens). The analytical sensitivity and specificity were both 100%. Interday reproducibility for fusion events was 94%; in comparison, intraday reproducibility was 90%. CONCLUSION: This multiple-gene fusion assay demonstrated appropriate sensitivity, specificity, and accuracy for clinical use. We anticipate that this assay will improve the diagnosis and management of patients with pediatric solid tumors.