Mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney generally shows low nuclear grade. MTSCC with high nuclear grade is relatively rare. In this article, we report two cases of MTSCC with Fuhrman grade 3. One case occurred in a 57-year-old Japanese female and the second case in a 49-year-old Caucasian female. Histologically, the tumors were composed of neoplastic cells with cuboidal or columnar and spindle morphology, and Fuhrman nuclear grade 3. The myxoid stroma was also observed. This stroma was positive for Alcian blue stain. Immunohistochemically, neoplastic cells of both cases were positive for AMACR, but negative for CD10 and RCC Ma. Ultrastructurally, tumorous cells of one case contained numerous mitochondria. In FISH analysis, many neoplastic cells of both cases demonstrated monosomy of chromosomes 15 and 22 and disomy of chromosomes 7 and 17. One of the two patients died of respiratory failure due to pleuritis carcinomatosa 48 months postoperatively. Finally, the pathologist should recognize that high grade MTSCC exists despite its rare frequency. FISH analysis may be helpful in establishing the diagnosis of this entity. Furthermore, we present the first report of a patient with MTSCC dying of distant metastasis.