Immunohistochemistry using monoclonal antibodies against human inhibin, a peptide hormone produced by ovarian granulosa cells to inhibit follicle-stimulating hormone (FSH), has been recently applied to diagnostic anatomic pathology. This investigation hypothesizes that inhibin immunohistochemistry will aid in the crucial clinical distinction between sex cord-stromal and other primary ovarian neoplasms. Available H&E slides and clinical information from a retrospective surgical series of 186 primary ovarian tumors were reviewed to verify diagnoses, and representative paraffin sections were immunostained with anti-inhibin (R1 monoclonal, Serotec, Kidlington, Oxford, UK). Immunoreactivity was graded as weak/strong (W/S), and the proportion of strong staining cells was coded as follows: S1 = <10%, S2 = 10%-50%, S3 = >50%, respectively. Inhibin immunoreactivity for 137 sex cord-stromal lesions was as follows: 100% of 66 granulosa cell tumors: 80% S3, 20% S2; 100% of 17 Sertoli-stromal tumors: 90% S3, 10% S2; 100% of 13 hyperplastic follicular/stromal lesions: 90% S3, 10% S2; 100% of six steroid cell tumors: 100% S3; 90% of 18 thecomas: 40% S3, 10% S2, 10% S1, 30% W; 0% of 12 fibromas, three myxomas, and two sclerosing stromal tumors. None (0 of 49) of the other ovarian neoplasms exhibited inhibin: 22 carcinomas, 12 carcinosarcomas, seven small cell carcinomas, six germ cell tumors, and two lymphomas. In the typical case, the distinction between sex cord-stromal and other ovarian neoplasms requires nothing more than routine pathological examination. In diagnostically challenging cases, our data indicate that inhibin immunohistochemistry is a very useful adjunct because granulosa and sertoli-stromal tumors are positive whereas other potential mimickers have been negative thus far.