We set out to ascertain whether uterine carcinosarcoma represents: (a) a “collision tumor,” i.e., a mixture of two histogenetically distinct malignant cell populations (endometrial carcinoma and sarcoma); (b) a “combination tumor” with both histological elements of common stem cell origin; or (c) a “composition tumor,” i.e., an endometrial carcinoma with reactive, atypical stroma. In in vitro cultures of human uterine carcinosarcoma, we could separate two distinct, different cell types and succeeded in establishing adenocarcinoma cell lines (HWUA-1 and HWUA-2) and sarcoma cell lines (HWUS-1, HWUS-1a, and HWUS-2). These cell lines grew well for over 10 months. HWUS-1a was hypertetraploid, HWUA-1 and HWUA-2 were pseudodiploid, and HWUS-1 and HWUS-2 were hyperdiploid. These cell lines were transplanted into the subcutis of BALB/c nude mice and produced tumors. HWUA-1 and HWUA-2 cells produced poorly differentiated adenocarcinoma, HWUS-1 and HWUS-2 produced poorly differentiated sarcoma, and HWUS-1a produced well-differentiated leiomyosarcoma. These results support the combination tumor theory and reject the composition tumor theory as the cause of carcinosarcoma.