We attempted to assess the clinical utility of squamous cell carcinoma antigen (SCC) for detecting squamous cell carcinoma arising in mature cystic teratoma of the ovary. SCC in serum from 16 patients with this malignancy and from 56 patients with mature cystic teratoma without malignancy was measured using radioimmunoassay. Serum SCC levels exceeded the cut-off of 2.0 ng/ml in 9 (56%) of the 16 patients with malignancy. This rate was significantly higher than that in the patients with nonmalignant mature cystic teratoma (9 to 56, 16%; p < 0.01). The positive rate for SCC was as low as 30% for stage I cancer. All cases in which the tumor size was > 500 cm3 had a positive response for SCC, whereas all other cases had a negative response (p < 0.001). SCC is useful as a tumor marker for this malignancy. However, the serum SCC level depends on the tumor volume, so it may not be suitable for early detection of small tumors.