The progression of ovarian carcinoma from stage I when it is confined to the ovaries and curable to disseminated abdominal disease, which is usually fatal, is poorly understood. An accurate understanding of this process is fundamental to designing, testing, and implementing an effective screening program for ovarian cancer. Pathologic features of the primary ovarian tumors in 41 FIGO stage I ovarian carcinomas were compared with those in 40 stage III carcinomas. The primary ovarian tumors in stage I cases, when compared with stage III, respectively, were significantly larger (15.4 versus 9.8 cm), were less frequently bilateral (12% versus 75%), more frequently contained a noninvasive component (88% versus 30%), had a higher proportion of a noninvasive component (42% versus 8%), and were more often nonserous (83% versus 20%) (P < 0.001 for all five comparisons). There are significant pathologic differences between the primary ovarian tumors in stage I and III ovarian carcinomas that are very difficult to explain by a simple temporal progression. These findings along with the growing body of literature suggest that early- and advanced-stage ovarian cancers are in many instances biologically different entities. This knowledge may have significant implications for our understanding of the biology of early- and advanced-stage ovarian cancer and therefore on the development of screening strategies for ovarian cancer.