Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small cell lung cancer (NSCLC), accounting for about 1% of cases. These tumors are characterized by their high malignancy and frequent resistance to chemotherapy, resulting in a worse prognosis compared to other NSCLC subtypes. Currently, there is no established therapeutic strategy for PSC. Recent advancements in targeted therapies have led to the development of ret proto-oncogene (RET) inhibitors, such as selpercatinib and pralsetinib, which have been approved for the treatment of RET fusion-positive NSCLC patients. Despite their effectiveness in RET fusion-positive NSCLC is observed, the efficacy of these inhibitors in PSC remains unclear. In this context, we present a case of metastatic PSC harboring de novo KIF5B-RET fusion. The patient responded to first-line trametinib treatment. These findings suggest that RET inhibitors could be a potential treatment option for metastatic PSC patients with RET fusion-positive tumors.