Objective. To determine if DNA ploidy, hormone receptors, vascular space invasion (VSI), perivascular lymphocytes (PVL), and the oncogenes HER-2/neu, p53, and bcl-2 are independent prognostic indicators for lymph node metastasis and cancer recurrence in clinical stage I endometrial carcinoma. Methods. Among 349 patients with clinical stage I endometrial cancer 31 patients either had lymph node metastases when surgically staged or developed recurrent cancer. Using a case-control matched-pair technique, controls were selected for each of 24 cases by matching for age, histological grade, depth of myometrial invasion, performance of node dissection, and use of adjuvant radiation therapy. In a blinded fashion a pathologist reviewed all histopathology, and all molecular tests were performed on paraffin-embedded tissue samples. Statistical analysis was performed by chi(2) and McNemar's tests. Results. VSI was the only histopathological factor significantly related to positive lymph nodes and cancer recurrence (P = 0.01), independent of grade and myometrial invasion. Aneuploidy, oncogene expression (p53, HER-2/neu, bcl-2), and hormone receptors were not significantly related to lymph node metastasis and cancer recurrence. Conclusions. The presence of vascular space invasion is a pathological factor independently associated with a risk of nodal metastasis and cancer recurrence in clinical stage I endometrial cancer. DNA ploidy, oncogene expression, and hormone receptor status do not have more predictive value than standard staging pathological criteria. (C) 1997 Academic Press.