Purpose: To investigate the prognostic value of pretreatment serum squamous cell carcinoma antigen (SCC-ag) levels in patients with cervical squamous cell carcinoma in relation to well-established conventional risk factors. Patients and Methods: Sere from 653 women treated for squamous cervical cancer between 1978 and 1994 were analyzed for the presence of SCC-og and related to clinicopathologic characteristics and patient outcome using univariate and multivariate analyses. Results: Increased pretreatment SCC-ag levels correlated strongly with unfavorable clinicopathologic characteristics (international Federation of Gynecology and Obstetrics [FIGO] stages IB to IV [P less than or equal to.00005]; stages IB and IV: tumor size [P =.0236], deep stromal infiltration [P =.00009], and lymph node metastasis [P =.0001]). After multivariate analysis, elevated pretreatment serum SCC-ag levels (P =.001), lesion size (P =.043), and vas cular invasion by tumor cells (P =.001) were independent predictors for the presence of lymph node metastases. In Cox regression analysis, controlling for SCC-ag, lesion size, grade, vascular invasion, depth of stromal infiltration, and lymph node status only the initial SCC-ag level had a significant independent effect on survival (P =.0152). Even in node-negative patients, the risk of recurrence was three times higher if the SCC-ag level was elevated before therapy. Conclusion: The determination of pretreatment serum SCC-ag level provides a new prognostic factor in early-stage disease, particularly in patients with small tumor size. In future trials to assess the value of new treatment strategies, pretreatment serum SCC-ag levels can be used to help identify patients with a poor prognosis. (C) 1996 by American Society of Clinical Oncology.