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BACKGROUND Thoracic SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4 (SMARCA4)-deficient undifferentiated tumor (SMARCA4-UT) is a rare and highly aggressive thoracic malignancy. It predominantly affects male smokers and typically arises in the mediastinum, where rapid tumor growth and early metastasis contribute to a poor prognosis. Recent evidence suggests that this tumor exhibits biological heterogeneity and variable responses to therapy, underscoring the need for further clinical characterization. CASE REPORT A 67-year-old man presented with dyspnea and superior vena cava syndrome. Computed tomography revealed a 7-cm mass in the anterior and superior mediastinum with suspected lymph node and bone metastases. Histological examination demonstrated a sheet-like proliferation of large atypical cells with rhabdoid features and necrosis. Immunohistochemical analysis showed loss of SMARCA4 (Brahma-related gene 1 [BRG1]) expression, positivity for cluster of differentiation 34 (CD34) and sex-determining region Y-box 2 (SOX2), weak epithelial membrane antigen expression, preserved integrase interactor 1 (INI1) expression, and negativity for other epithelial markers, fulfilling the diagnostic criteria for SMARCA4-UT. Despite palliative radiotherapy and combination immunotherapy with nivolumab and ipilimumab, the tumor rapidly progressed. The patient developed grade 4 drug-induced pneumonitis; transient stabilization was achieved, but his condition deteriorated. He died 6 months after disease onset. Autopsy revealed widespread metastases with minimal therapeutic effect, highlighting the aggressive clinical course and treatment resistance. CONCLUSIONS SMARCA4-UT is a highly aggressive tumor requiring comprehensive immunohistochemical evaluation for accurate diagnosis. This case highlights the limited efficacy of immune checkpoint inhibitors in a PD-L1-negative setting and underscores the need for more effective therapeutic strategies.