ABSTRACT Background Mesenchymal neoplasms characterized by ALK fusions mainly include inflammatory myofibroblastic tumors (IMTs) and epithelioid fibrous histiocytomas (EFHs). More recently, ALK ‐rearranged mesenchymal tumors that are not IMTs or EFHs, characterized by S100 and CD34 coexpression, have been reported in a few small series and isolated case reports. The neoplasms present a broad clinicopathological spectrum and variable biological behavior. Case Presentation Here, we report the case of an 11‐year‐old girl with a giant mesenchymal neoplasm in her left thoracic cavity. Pathological biopsy revealed that the tumor was composed of monomorphic spindle cells arranged in a fascicular growth pattern with extensive necrosis and coexpression of S100 and CD34; subsequently, PLEKHH2 :: ALK fusion was identified via next‐generation sequencing (NGS). The patient underwent tumor resection via thoracoscopy. The specimen from radical resection indicated that the tumor was heterogeneous. Some tumor cells showed moderate to severe atypia with increased mitosis and necrosis, suggesting that the neoplasm had overtly malignant features and may be associated with an aggressive clinical course. The patient developed brain metastasis 3 months after surgery and subsequently responded well to targeted therapy with the ALK inhibitor alectinib. Conclusions Our findings indicate that ALK ‐rearranged mesenchymal neoplasms with fibrosarcoma‐like features, particularly those associated with elevated mitotic activity or tumor necrosis, should be classified as high grade in pathology reports. In addition, this case also demonstrated that neoadjuvant therapy may be a better treatment strategy compared to upfront surgery for ALK ‐rearranged mesenchymal neoplasms with a relatively high tumor burden.