Abstract
Bone and soft-tissue sarcomas encompass over 70 histologic subtypes, posing diagnostic challenges due to overlapping characteristics. Molecular analyses, such as fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction (RT-PCR), aid in identifying specific genomic alterations but are often limited, particularly when prior histological findings are inconclusive. Next-generation sequencing (NGS) offers high-throughput testing via a targeted sequencing panel, addressing these limitations. This case series highlights the utility of NGS in diagnosing two pediatric patients with immunobiologically ambiguous Ewing sarcoma (ES) and clear cell sarcoma (CCS), emphasizing its role as a powerful tool in solid tumor diagnosis.