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Mucinous tubular and spindle cell carcinoma (MTSCC) is an uncommon renal tumor with characteristic morphologic features but overlapping immunophenotype with papillary renal cell carcinoma. Recent genomic and transcriptomic analysis of MTSCC has uncovered recurrent chromosomal losses and frequent biallelic alteration of Hippo pathway genes, resulting in increased YAP1 nuclear expression. In this article, we describe a case of MTSCC and review the pertinent clinical, morphologic, immunohistochemical, and molecular findings of this uncommon kidney tumor. In the era of personalized medicine, increased pathologic recognition of MTSCC may facilitate targeted therapeutic approaches (ie, the YAP1 small molecule inhibitor verteporfin) for rare patients with aggressive tumors.