There is a wide range of aggressiveness of endometrial tumors, some being indolent and easily treated while others metastasize and prove fatal. The authors used data from three population-based, case-control studies to determine if etiologic factors differ for aggressive disease. Interview data were obtained from 1,304 female residents of western Washington State who were 45-74 years of age and diagnosed with endometrial cancer during 1985-1991, 1994-1995, and 1997-1999 and from 1,779 controls who were of similar ages and selected primarily by random digit dialing. As a means of gauging aggressiveness, tumor characteristics were abstracted from the population-based cancer registry that serves western Washington State. The risk of endometrial cancer among long-term users (> or = 8 years) of unopposed estrogens was particularly high for the least aggressive tumors (odds ratio = 18.6, 95% confidence interval: 12.2, 28.6) but was elevated for moderate and highly aggressive tumors as well (odds ratios = 6.6 and 7.1, respectively). Women who were obese, had a history of diabetes, and had fewer than two children were also at increased risk, regardless of tumor aggressiveness, while oral contraceptive users were at decreased risk of only relatively more aggressive disease. In general, a woman's risk of endometrial cancer appears to be influenced by similar risk factors regardless of disease severity.