The solid variant of papillary renal cell carcinoma (PRCC) is distinguishable genetically from mucinous tubular and spindle cell carcinoma (MTSC) of the kidney by the presence of trisomy for chromosomes 7 and 17; however, at the morphologic and immunohistochemical levels, these neoplasms overlap significantly. The key morphologic feature distinguishing these two is thought to be the low grade of the spindle cell areas of MTSC; spindle cell areas in PRCC generally signify sarcomatoid change and are high grade. We report 5 cases of PRCC with low-grade spindle cell foci, closely mimicking MTSC. All patients were male, and ranged in age from 17 to 68 years. All tumors were predominantly solid, featuring compact areas of low-grade spindle cells lining thin, angulated tubules. Mucinous stroma was not appreciated in any case. All cases were diffusely immunoreactive for cytokeratin 7, and focally CD10 positive. All 5 cases showed trisomy of chromosome 7, and 3 of 5 showed trisomy of chromosome 17 by fluorescence in situ hybridization, supporting classification as PRCC. These cases further reported morphologic overlap between MTSC and PRCC. Before a diagnosis of metastatic MTSC or MTSC with unusual morphology is rendered, the possibility of PRCC with low-grade spindle cell foci should be considered. Fluorescence in situ hybridization analysis effectively separates these morphologically very similar yet genetically distinctive entities. Copyright © 2008 by Lippincott Williams & Wilkins.