OBJECTIVES: This study was conducted to define the role of microsatellite instability (MSI) in cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma (SCC) of the cervix. We also tested the validity of using markers recommended for MSI study in colonic carcinoma by the National Cancer Institute (NCI) for cervical neoplasm. METHODS: Twenty normal cervical, 24 low-grade CIN (CIN-L), 59 high-grade CIN (CIN-H), and 93 SCC tissues were examined for MSI after microdissection. A polymerase chain reaction based MSI detection was performed using five markers recommended by the NCI for colonic cancer (panel one) as well as five other markers (panel two) found to be informative in earlier studies. High-frequency MSI (MSI-H) was defined as instability in > or = 2 of 5 loci if one panel was used and > or = 30% of loci when more than five loci were used. Low-frequency MSI (MSI-L) was diagnosed if instability was noted but did not meet the criteria of MSI-H. Findings were correlated with clinicopathologic information. RESULTS: The combined use of panel one and two markers showed no MSI in normal cervical or CIN-L tissue, MSI-L in 1 CIN-H (1.7%), MSI-L in 16 (17.2%), and MSI-H in 11 (11.8%) SCC, respectively. The NCI-recommended panel alone detected 19 of 27 MSI-positive SCC. MSI-positive was not related to patient age, disease stage, and tumor grade. The overall survival of MSI-positive patients was significantly worse than that of microsatellite stable patients (P = 0.02). An increasing trend of MSI-H rate with higher disease stages was noted (P = 0.035) but MSI-H was not associated with poor prognosis. CONCLUSIONS: The NCI recommended panel of markers might not be useful in MSI study for SCC and using more than five markers improves the MSI detection. MSI is rare in cervical dysplasia but is present in a subset of SCC. The association between MSI-positivity and prognosis awaits future confirmation.