PURPOSE: The aim of this study was to define the prognostic role of microsatellite status in 65 stage I-II primary sporadic endometrioid endometrial adenocarcinoma (EEA) patients. PATIENTS AND METHODS: Familiarity for neoplasia was ascertained in all patients on the basis of a questionnaire. Microsatellite status was assessed by matching normal and tumoral DNA probed for five dinucleotide repeats and one mononucleotide repeat marker. Microsatellite status was analyzed in relation to clinicopathologic characteristics of the patients and length of disease-free survival (DFS). RESULTS: Eleven tumors (17%) of 65 had instability at two or more loci and were considered as unstable or microsatellite instability (MI). Tumors with no instability or instability at one locus were classified as microsatellite stable (MS). The percentage of MI was significantly higher in poorly than in well to moderately differentiated tumors (50% v 9%; P = .003). The 5-year DFS rate of MI patients was 63% (95% confidence interval [CI], 35% to 91%) versus 96% (95% CI, 91% to 101%) of MS patients (P = .0004). In multivariate analysis, only the presence of MI, stage II of disease, and depth of myometrial invasion greater than 50% retained independent prognostic roles. CONCLUSION: The assessment of microsatellite status may provide useful information for preoperative prognostic characterization of stage I-II primary sporadic EEA patients in which more individualized treatment options can be attempted.