This study compares morphometric features of endometrial papillary carcinomas, serous and endometrioid types, in an effort identify characteristics that predict clinical outcome. Fifty-one consecutive patients with papillary carcinoma were identified at NYU Medical Center from January 1979 through December 1991 and were followed through 1994. Morphologic analysis was conducted by investigators (R.D. and K.M.) blinded as to original diagnosis, depth of invasion, stage and outcome. Of 25 variables analyzed, six were significantly associated with reduced survival, namely marked nuclear pleomorphism, multinucleated cells, hobnail cells, psammoma bodies, uneven papillary borders, and inflammation. Serous carcinomas showed a highly significant (p = 0.0001) association with reduced length of recurrence-free survival, with a median survival of 27 months (mean +/- SE, 38.9 +/- 7.0) versus 95 months (106.7 +/- 15.3) for patients with endometrioid types. Of six morphologic characteristics that correlated with reduced recurrence-free survival by univariate analyses, only one, nuclear pleomorphism, showed a significant association with an adverse outcome in a multivariate regression analysis (p = 0.0020), even after adjustment for the effect of tumor stage. Therefore, we believe that the presence of marked nuclear pleomorphism should serve as the major criterion for making a diagnosis of serous carcinoma. In tumors with moderate nuclear pleomorphism, a diagnosis of serous carcinoma is aided by the presence of multinucleated cells, uneven papillary borders, high nuclear/cytoplasmic ratio, apical location of the nucleus, and hobnail cells. These features were significantly associated with a diagnosis of serous carcinoma in our patients.