Mixed epithelial and stromal tumor of the kidney is an uncommon complex neoplasm, and previous studies have included only a modest number of cases and have left gaps in our understanding of its morphology. We analyzed 53 tumors (46 F, median age: 49 y), collecting data on gross, histologic, and immunohistochemical features. The most common gross appearance was solid and cystic (47%). Hypocellular fibrous and cellular spindle cell stroma were the most common stromal types, followed by smooth muscle differentiation, edematous stroma, and adipose tissue. Hypocellular fibrous stroma and adipose tissue were more common in larger tumors (P=0.003 and 0.04, respectively) and cellular spindle cell stroma in smaller tumors (P=0.0009). Combinations of diverse stromal elements were common: roughly 50% of tumors contained >4 types of stroma. With regard to epithelium, tiny crowded and branching glands were present in 60% of tumors. Round glands lined by tall cuboidal epithelium, reminiscent of thyroid follicles, spatulate papillae reminiscent of phyllodes tumor, glands reminiscent of nephrogenic adenoma, and complex papillae were also frequently found. Combinations of diverse epithelial elements were common: 64% of tumors contained >4 types of epithelium. All of the tumors except 1 were positive for smooth muscle actin in the stroma. Desmin and caldesmon expression were more variable. Stains for progesterone and estrogen receptors showed positivity in the stromal component in 85% and 73% of tumors, respectively. CD10 and CD34 immunolabeling were restricted to pericystic spindle cells. No tumor expressed inhibin. In summary, this study demonstrates a strong tendency for mixed epithelial and stromal tumors to contain multiple types of stroma and epithelium and comprehensively analyzes the immunohistochemical profile.