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Objective: To determine the clinical significance of serum follistatin levels in women with an ovarian endometrioma. Materials and methods: This is a prospective study of 89 women, 56 with an ovarian endometrioma (endometrioma group) and 33 with a benign ovarian cyst (control group) who underwent laparoscopic excision. Age, parity, body mass index, serum CA-125, serum CA 19-9, and serum follistatin levels were determined for all participants and evaluated as potential prognostic factors prior to laparoscopic cystectomy. Results: There were no significant differences in demographic factors between the endometrioma group and the control group. However, serum follistatin levels were significantly higher in the endometrioma group (9350 ± 895 pg/mL vs. control group 725 ± 72 pg/mL, p < 0.05). The optimal diagnostic cut-off values (sensitivity and specificity) of CA-125, CA 19-9, and follistatin for ovarian endometrioma were 23.2 IU/mL (82.14% and 72.73%), 30.14 IU/mL (45.28% and 87.50%), and 2350 pg/mL (53.7% and 60.61%), respectively. Conclusion: Despite the increased serum follistatin levels in patients with ovarian endometrioma, CA-125 was determined to be a more sensitive and specific marker than follistatin for the diagnosis of ovarian endometrioma and endometriosis.