The prognostic implication of benign and malignant squamous differentiation was examined in 267 consecutive patients with stage I endometrial carcinoma. Patients with adenosquamous carcinoma had a significantly poorer ten-year survival rate (54.7%) than patients with adenocarcinoma (70.5%) or adenoacanthoma (87.4%). This was related to a tendency for adenosquamous carcinoma to be associated with poorly differentiated glandular elements and to deeply invade the myometrium. The mean depth of myometrial penetration was 57% for adenosquamous carcinoma compared with 24% for adenocarcinoma and 19% for adenoacanthoma. To examine the prognostic significance of malignant squamous differentiation independently of the grade of the associated glandular component, the subgroup of patients with well-differentiated adenocarcinoma was compared. Patients with well-differentiated adenosquamous carcinoma persisted in having a worse prognosis (58.3% ten-year survival rate), compared with adenocarcinoma (84.3% ten-year survival rate), which was explained by the propensity of adenosquamous carcinoma to deeply invade the myometrium.