CD99, a marker for MIC-2, reacts with normal Sertoli cells and granulosa cells. We investigated CD99 expression in the development of normal ovary and testis as well as in 25 sex cord-stromal tumors (SCSTs), 7 epithelial neoplasms, and 6 germ cell tumors. Normal Sertoli cells and mature granulosa cells showed 3+ staining with CD99. Pregranulosa cells of primordial follicles were negative. All of the eight Sertoli-Leydig cell tumors were positive with antibody to CD99, with the well-differentiated tumors showing the greatest degree of staining intensity. Reactivity of 2+ to 3+ with CD99 was observed in all of the 11 granulosa cell tumors and in yolk sac components of the germ cell tumors investigated. All of the poorly differentiated carcinomas were negative with CD99. We concluded that CD99 might be a useful marker for SCSTs and that its degree of reactivity correlates with the degree of differentiation in Sertoli-Leydig cell tumors. Additionally, CD99 might aid in distinguishing granulosa cell tumors of the ovary from poorly differentiated carcinomas.