The distinction between malignant mixed müllerian tumor (MMMT) of the female genital tract and poorly differentiated endometrial adenocarcinoma (EA) is sometimes difficult and arbitrary. Although several studies have described the immunohistochemical profile of MMMT and EA, the results have varied, and controversy regarding the histogenetic relationship between them remains. The authors examined the histologic characteristics and immunohistochemistry of 31 formalin-fixed paraffin-embedded MMMTs from a variety of female genital tract sites with a panel of monoclonal and polyclonal antibodies using the avidin-biotin-peroxidase complex (ABC) method. Eighteen neoplasms were homologous and 13 were heterologous; the average patient age was 67 years. In all cases the epithelial component stained for keratin (K), whereas the stromal component stained in 48%; vimentin (V) was detected in the epithelial component in 35% and the stromal component in 81%. Myoglobin (M) detected rhabdomyoblasts in three of five cases tested; desmin (D) was found in five of six and actin (A) in all six cases with skeletal muscle. Overall, A stained the stromal components in 45% of cases, whereas none of the epithelial components stained. The coexpression of K and V in the epithelial component of 35% of cases and in the stromal component of 48% of cases led the authors to conclude that the immunoprofile of MMMT broadly overlaps with that of EA and, independent of morphologic findings, it is often not reliable or useful in distinguishing between the two. Furthermore, the variable immunoprofile suggests that MMMT may be a histogenetically heterogeneous group of neoplasms, including both carcinomas (metaplastic, sarcomatoid) as well as true carcinosarcomas. Although A detected rhabdomyoblasts in all cases, it also stained neoplastic mesenchymal elements in eight more cases, suggesting the presence of smooth muscle or myofibroblasts in the stroma of some MMMTs.